Scholars@Duke
David Charles Montefiori

David Charles Montefiori

Professor in Surgery
Surgery, Surgical Sciences
monte@duke.edu
Box 2926 Med Ctr, Durham, NC
Surgical Oncology Res Fac, Durham, NC 27710

Selected Publications

HVTN 123: A Phase 1, Randomized Trial Comparing Safety and Immunogenicity of CH505TF gp120 Produced by Stably and Transiently Transfected Cell Lines.

Journal Article J Infect Dis · December 13, 2024 Utilizing transiently transfected cell lines could significantly reduce manufacturing timelines for protein subunit vaccines. This trial compared safety and immunogenicity of human immunodeficiency virus (HIV) envelope CH505TF gp120 vaccines produced by up ... Full text Link to item Cite

Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques.

Journal Article bioRxiv · November 29, 2024 During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccinati ... Full text Link to item Cite

Neonatal immunity associated with heterologous HIV-1 neutralizing antibody induction in SHIV-infected Rhesus Macaques.

Journal Article Nat Commun · November 27, 2024 The details of the pediatric immune system that supports induction of antibodies capable of neutralizing geographically-diverse or heterologous HIV-1 is currently unclear. Here we explore the pediatric immune environment in neonatal macaque undergoing Simi ... Full text Link to item Cite

Short CDRL1 in intermediate VRC01-like mAbs is not sufficient to overcome key glycan barriers on HIV-1 Env.

Journal Article J Virol · October 22, 2024 UNLABELLED: VRC01-class broadly neutralizing antibodies (bnAbs) have been isolated from people with HIV-1, but they have not yet been elicited by vaccination. They are extensively somatically mutated and sometimes accumulate CDRL1 deletions. Such indels ma ... Full text Link to item Cite

Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies.

Journal Article J Exp Med · October 7, 2024 Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 sig ... Full text Link to item Cite

Mosaic and mixed HIV-1 glycoprotein nanoparticles elicit antibody responses to broadly neutralizing epitopes.

Journal Article PLoS Pathog · October 2024 An effective human immunodeficiency virus 1 (HIV-1) vaccine will most likely have to elicit broadly neutralizing antibodies (bNAbs) to overcome the sequence diversity of the envelope glycoprotein (Env). So far, stabilized versions of Env, such as SOSIP tri ... Full text Link to item Cite

Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site.

Journal Article Sci Immunol · August 30, 2024 Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diver ... Full text Link to item Cite

Immunization with germ line-targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques.

Journal Article Sci Immunol · August 30, 2024 Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitati ... Full text Link to item Cite

Interim Report of the Reactogenicity and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 XBB-Containing Vaccines.

Journal Article J Infect Dis · August 16, 2024 BACKGROUND: Monovalent Omicron XBB.1.5-containing vaccines were approved for coronavirus disease 2019 (COVID-19) 2023-2024 immunizations. METHODS: This ongoing, open-label, phase 2/3 study evaluated messenger RNA (mRNA)-1273.815 monovalent (50-µg Omicron X ... Full text Link to item Cite

SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition.

Journal Article Mol Cell · July 25, 2024 A recombinant lineage of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for the ... Full text Link to item Cite

Priming antibody responses to the fusion peptide in rhesus macaques.

Journal Article NPJ Vaccines · July 12, 2024 Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effecti ... Full text Link to item Cite

Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.

Journal Article Cell · June 6, 2024 A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposom ... Full text Link to item Cite

SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial.

Journal Article Lancet Microbe · June 2024 BACKGROUND: A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 (SpFN/ALFQ) has shown protective efficacy in anim ... Full text Link to item Cite

Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial.

Journal Article PLoS Med · June 2024 BACKGROUND: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention effi ... Full text Link to item Cite

Stabilized trimeric peptide immunogens of the complete HIV-1 gp41 N-heptad repeat and their use as HIV-1 vaccine candidates.

Journal Article Proc Natl Acad Sci U S A · May 28, 2024 Efforts to develop an HIV-1 vaccine include those focusing on conserved structural elements as the target of broadly neutralizing monoclonal antibodies. MAb D5 binds to a highly conserved hydrophobic pocket on the gp41 N-heptad repeat (NHR) coiled coil and ... Full text Link to item Cite

Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains.

Journal Article Nat Commun · May 21, 2024 The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent ... Full text Link to item Cite

Innate protection against intrarectal SIV acquisition by a live SHIV vaccine.

Journal Article JCI Insight · May 21, 2024 Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine again ... Full text Link to item Cite

Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays.

Journal Article Sci Transl Med · May 15, 2024 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability of newly arising variants to escape the immune response. A surveillance system necessitates an understanding of differences in ne ... Full text Link to item Cite

Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.

Journal Article Cell Host Microbe · May 8, 2024 A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbabl ... Full text Link to item Cite

Safety and immunogenicity of a polyvalent DNA-protein HIV vaccine with matched Env immunogens delivered as a prime-boost regimen or coadministered in HIV-uninfected adults in the USA (HVTN 124): a phase 1, placebo-controlled, double-blind randomised controlled trial.

Journal Article The lancet. HIV · May 2024 BackgroundAn effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA-prot ... Full text Cite

Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Subvariant Neutralization Following a Primary Vaccine Series of NVX-CoV2373 and BNT162b2 Monovalent Booster Vaccine.

Journal Article Open Forum Infect Dis · February 2024 We evaluated the immunologic response to a novel vaccine regimen that included 2 doses of NVX-CoV2373 (Novavax) followed by 1 dose of BNT162b2 (Pfizer-BioNTech) monovalent booster vaccine. A durable neutralizing antibody response to Omicron BA.4/BA.5 and B ... Full text Link to item Cite

Phase II prefusion non-stabilised Covid-19 mRNA vaccine randomised study.

Journal Article Sci Rep · January 29, 2024 ChulaCov19 mRNA vaccine demonstrated promising phase 1 results. Healthy adults aged 18-59 years were double-blind randomised 4:1 to receive two intramuscular doses of ChulaCov19 50 µg or placebo. Primary endpoints were safety and microneutralization antibo ... Full text Link to item Cite

Development of LIBRA-seq for the guinea pig model system as a tool for the evaluation of antibody responses to multivalent HIV-1 vaccines.

Journal Article J Virol · January 23, 2024 Consistent elicitation of serum antibody responses that neutralize diverse clades of HIV-1 remains a primary goal of HIV-1 vaccine research. Prior work has defined key features of soluble HIV-1 Envelope (Env) immunogen cocktails that influence the neutrali ... Full text Link to item Cite

Prevention efficacy of the broadly neutralizing antibody VRC01 depends on HIV-1 envelope sequence features.

Journal Article Proc Natl Acad Sci U S A · January 23, 2024 In the Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081), prevention efficacy (PE) of the monoclonal broadly neutralizing antibody (bnAb) VRC01 (vs. placebo) against HIV-1 acquisition diagnosis varied according to the HIV- ... Full text Link to item Cite

Contralateral second dose improves antibody responses to a 2-dose mRNA vaccination regimen.

Journal Article J Clin Invest · January 16, 2024 BACKGROUNDVaccination is typically administered without regard to site of prior vaccination, but this factor may substantially affect downstream immune responses.METHODSWe assessed serological responses to initial COVID-19 vaccination in baseline seronegat ... Full text Link to item Cite

A Randomised Clinical Trial of the Safety and Pharmacokinetics of VRC07-523LS Administered via Different Routes and Doses (HVTN 127/HPTN 087).

Journal Article medRxiv · January 11, 2024 BACKGROUND: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the only bnAb HIV prevention efficacy studies to date, the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administer ... Full text Link to item Cite

Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.

Journal Article Cell · January 4, 2024 The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glyca ... Full text Link to item Cite

Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1-2 randomized double-blind placebo-controlled trial.

Journal Article PLOS Glob Public Health · 2024 Induction of broad, durable immune responses is a challenge in HIV vaccine development. HVTN 100 Part A administered subtype C-containing ALVAC-HIV at months 0 and 1, and ALVAC-HIV with bivalent subtype C gp120/MF59 at months 3, 6 and 12. As IgG binding an ... Full text Link to item Cite

Immunogenicity of a 2-Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

Journal Article J Infect Dis · December 20, 2023 We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the ser ... Full text Link to item Cite

High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials.

Journal Article Nat Commun · December 14, 2023 The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a ... Full text Link to item Cite

Stochastic interventional approach to assessing immune correlates of protection: Application to the COVE messenger RNA-1273 vaccine trial.

Journal Article Int J Infect Dis · December 2023 BACKGROUND: Stochastic interventional vaccine efficacy (SVE) analysis is a new approach to correlate of protection (CoP) analysis of a phase III trial that estimates how vaccine efficacy (VE) would change under hypothetical shifts of an immune marker. METH ... Full text Link to item Cite

Host immunity associated with spontaneous suppression of viremia in therapy-naïve young rhesus macaques following neonatal SHIV infection.

Journal Article J Virol · November 30, 2023 Despite the advent of highly active anti-retroviral therapy, people are still dying from HIV-related causes, many of whom are children, and a protective vaccine or cure is needed to end the HIV pandemic. Understanding the nature and activation states of im ... Full text Open Access Link to item Cite

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

Journal Article Nat Commun · November 30, 2023 Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815 ... Full text Link to item Cite

A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates.

Journal Article Nat Commun · November 4, 2023 Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen k ... Full text Link to item Cite

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells.

Journal Article Vaccines (Basel) · October 30, 2023 At the heart of the DNA/ALVAC/gp120/alum vaccine's efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine eff ... Full text Link to item Cite

Human CD4-Binding Site Antibody Elicited by Polyvalent DNA Prime-Protein Boost Vaccine Neutralizes Cross-Clade Tier-2-HIV Strains.

Journal Article Res Sq · October 20, 2023 The vaccine elicitation of HIV-neutralizing antibodies with tier-2-neutralization breadth has been a challenge. Here, we report the isolation and characteristics of a CD4-binding site specific monoclonal antibody, HmAb64, from a human volunteer immunized w ... Full text Link to item Cite

Safety and immunogenicity of a recombinant oligomeric gp145 subtype C Env protein (gp145 C.6980) HIV vaccine candidate in healthy, HIV-1-uninfected adult participants in the US.

Journal Article Vaccine · October 6, 2023 BACKGROUND: An approach to a preventive HIV vaccine is induction of effective broadly neutralizing antibodies (bnAbs) and effector binding antibodies (bAbs). Preclinical studies suggest that trimeric envelope (Env) proteins may elicit nAbs, which led to th ... Full text Link to item Cite

Mapping SARS-CoV-2 antigenic relationships and serological responses.

Journal Article Science · October 6, 2023 During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns of cr ... Full text Open Access Link to item Cite

Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial.

Journal Article Lancet HIV · October 2023 BACKGROUND: Preclinical and clinical studies suggest that combinations of broadly neutralising antibodies (bnAbs) targeting different HIV envelope epitopes might be required for sufficient prevention of infection. We aimed to evaluate the dual and triple a ... Full text Link to item Cite

Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial.

Journal Article Viruses · September 29, 2023 The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibod ... Full text Link to item Cite

Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera.

Journal Article bioRxiv · September 27, 2023 The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human ... Full text Link to item Cite

Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 bivalent COVID-19 mRNA vaccines: phase 2/3 trial interim results.

Journal Article Nat Med · September 2023 This ongoing, open-label, phase 2/3 trial compared the safety and immunogenicity of the Omicron BA.4/BA.5-containing bivalent mRNA-1273.222 vaccine with the ancestral Wuhan-Hu-1 mRNA-1273 as booster doses. Two groups of adults who previously received mRNA- ... Full text Link to item Cite

Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.

Journal Article Nat Med · September 2023 Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed ... Full text Link to item Cite

Three-month antibody persistence of a bivalent Omicron-containing booster vaccine against COVID-19.

Journal Article Nat Commun · August 23, 2023 We previously presented day 29 interim safety and immunogenicity results from a phase 2/3 study (NCT04927065) comparing the Omicron-BA.1-containing bivalent vaccine mRNA-1273.214 (50-µg) to the 50-µg mRNA-1273 booster in adults who previously received the ... Full text Link to item Cite

Mutational basis of serum cross-neutralization profiles elicited by infection or vaccination with SARS-CoV-2 variants.

Journal Article bioRxiv · August 14, 2023 UNLABELLED: A series of SARS-CoV-2 variants emerged during the pandemic under selection for neutralization resistance. Convalescent and vaccinated sera show consistently different cross-neutralization profiles depending on infecting or vaccine variants. To ... Full text Link to item Cite

Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques.

Journal Article Nat Commun · August 8, 2023 Route of immunization can markedly influence the quality of immune response. Here, we show that intradermal (ID) but not intramuscular (IM) modified vaccinia Ankara (MVA) vaccinations provide protection from acquisition of intravaginal tier2 simian-human i ... Full text Link to item Cite

Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants.

Journal Article NPJ Vaccines · July 11, 2023 As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dos ... Full text Link to item Cite

Pharmacokinetic serum concentrations of VRC01 correlate with prevention of HIV-1 acquisition.

Journal Article EBioMedicine · July 2023 BACKGROUND: The phase 2b proof-of-concept Antibody Mediated Prevention (AMP) trials showed that VRC01, an anti-HIV-1 broadly neutralising antibody (bnAb), prevented acquisition of HIV-1 sensitive to VRC01. To inform future study design and dosing regimen s ... Full text Link to item Cite

Plain Language Summary of a Clinical Trial Evaluating mRNA-1273, Moderna's mRNA-Based COVID-19 Vaccine, in Children 6 Through 11 Years of Age

Journal Article Future Virology · July 1, 2023 What is this summary about? The PLSP summarizes results from the phase 2/3 KidCOVE trial examining mRNA-1273 (Moderna's COVID-19 vaccine) in children 6 through 11 years of age. What were the results? This study reviewed results from two parts of the KidCOV ... Full text Cite

Focusing antibody responses to the fusion peptide in rhesus macaques.

Journal Article bioRxiv · June 27, 2023 Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effecti ... Full text Link to item Cite

Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration.

Journal Article Nat Commun · June 17, 2023 While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist for preventative monoclonal antibodies. In this work, nAb titers were assessed as correlat ... Full text Link to item Cite

Immunogenicity of a Two Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

Journal Article medRxiv · June 10, 2023 In this brief report, we compare the magnitude and durability of the serologic response of one versus two doses (separated by 56 days) of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. ... Full text Link to item Cite

Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials.

Journal Article PLoS Pathog · June 2023 The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 ... Full text Link to item Cite

Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response.

Journal Article PLoS Pathog · May 2023 The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% vaccine efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates of decreased infection risk. New strategies to increase ma ... Full text Link to item Cite

Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial.

Journal Article Sci Transl Med · April 19, 2023 The best assay or marker to define mRNA-1273 vaccine-induced antibodies as a correlate of protection (CoP) is unclear. In the COVE trial, participants received two doses of the mRNA-1273 COVID-19 vaccine or placebo. We previously assessed IgG binding antib ... Full text Link to item Cite

Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults: A Phase 1/2a Study.

Journal Article J Infect Dis · April 18, 2023 BACKGROUND: Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV. METHODS: This placebo-controlled, double-blind, phase 1/2a study enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were rando ... Full text Link to item Cite

Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.

Journal Article Cell Rep Med · April 18, 2023 Targeting germline (gl-) precursors of broadly neutralizing antibodies (bNAbs) is acknowledged as an important strategy for HIV-1 vaccines. The VRC01-class of bNAbs is attractive because of its distinct genetic signature. However, VRC01-class bNAbs often r ... Full text Link to item Cite

Cellular and humoral responses to an HIV DNA prime by electroporation boosted with recombinant vesicular stomatitis virus expressing HIV subtype C Env in a randomized controlled clinical trial.

Journal Article Vaccine · April 17, 2023 BACKGROUND: HIV subtypes B and C together account for around 60% of HIV-1 cases worldwide. We evaluated the safety and immunogenicity of a subtype B DNA vaccine prime followed by a subtype C viral vector boost. METHODS: Fourteen healthy adults received DNA ... Full text Link to item Cite

Neonatal SHIV infection in rhesus macaques elicited heterologous HIV-1-neutralizing antibodies.

Journal Article Cell Rep · March 28, 2023 Infants and children infected with human immunodeficiency virus (HIV)-1 have been shown to develop neutralizing antibodies (nAbs) against heterologous HIV-1 strains, characteristic of broadly nAbs (bnAbs). Thus, having a neonatal model for the induction of ... Full text Link to item Cite

Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251.

Journal Article Nat Commun · March 7, 2023 Human immunodeficiency virus (HIV) is a mucosally transmitted virus that causes immunodeficiency and AIDS. Developing efficacious vaccines to prevent infection is essential to control the epidemic. Protecting the vaginal and rectal mucosa, the primary rout ... Full text Link to item Cite

Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later.

Journal Article Sci Transl Med · March 2023 The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emergi ... Full text Link to item Cite

A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.

Journal Article mBio · February 28, 2023 HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in ... Full text Link to item Cite

Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.

Journal Article J Clin Invest · February 15, 2023 BACKGROUNDMosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models.METHODSThis double-blind randomi ... Full text Link to item Cite

HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC.

Journal Article Nat Commun · February 2, 2023 The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to vaccination. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on ... Full text Link to item Cite

Mid-titer human convalescent plasma administration results in suboptimal prophylaxis against SARS-CoV-2 infection in rhesus macaques.

Journal Article Front Immunol · 2023 INTRODUCTION: ARS-CoV-2 is a respiratory pathogen currently causing a worldwide pandemic, with resulting pathology of differing severity in humans, from mild illness to severe disease and death. The rhesus macaque model of COVID-19 was utilized to evaluate ... Full text Link to item Cite

Correction: HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers.

Journal Article PLoS One · 2023 [This corrects the article DOI: 10.1371/journal.pone.0181886.]. ... Full text Link to item Cite

Prediction of serum HIV-1 neutralization titers of VRC01 in HIV-uninfected Antibody Mediated Prevention (AMP) trial participants.

Journal Article Hum Vaccin Immunother · December 31, 2022 VRC01 is being evaluated in the AMP efficacy trials, the first assessment of a passively administered broadly neutralizing monoclonal antibody (bnAb) for HIV-1 prevention. A key analysis will assess serum VRC01-mediated neutralization as a potential correl ... Full text Link to item Cite

Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques.

Journal Article Viruses · December 17, 2022 HIV vaccine mediated efficacy, using an expanded live attenuated recombinant varicella virus-vectored SIV rSVV-SIVgag/env vaccine prime with adjuvanted SIV-Env and SIV-Gag protein boosts, was evaluated in a female rhesus macaques (RM) model against repeate ... Full text Link to item Cite

Vaccination induces HIV broadly neutralizing antibody precursors in humans.

Journal Article Science · December 2, 2022 Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled p ... Full text Link to item Cite

Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates.

Journal Article NPJ Vaccines · November 25, 2022 The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial c ... Full text Link to item Cite

Adjuvants influence the maturation of VRC01-like antibodies during immunization.

Journal Article iScience · November 18, 2022 Once naive B cells expressing germline VRC01-class B cell receptors become activated by germline-targeting immunogens, they enter germinal centers and undergo affinity maturation. Booster immunizations with heterologous Envs are required for the full matur ... Full text Link to item Cite

Humoral Immunogenicity of the mRNA-1273 Vaccine in the Phase 3 Coronavirus Efficacy (COVE) Trial.

Journal Article J Infect Dis · November 11, 2022 BACKGROUND: Messenger RNA (mRNA)-1273 vaccine demonstrated 93.2% efficacy against coronavirus disease 2019 (COVID-19) in the Coronavirus Efficacy (COVE) trial. The humoral immunogenicity results are now reported. METHODS: Participants received 2 mRNA-1273 ... Full text Link to item Cite

Correlation of Binding and Neutralizing Antibodies against SARS-CoV-2 Omicron Variant in Infection-Naïve and Convalescent BNT162b2 Recipients.

Journal Article Vaccines (Basel) · November 11, 2022 In vaccine clinical trials, both binding antibody (bAb) levels and neutralization antibody (nAb) titers have been shown to be correlates of SARS-CoV-2 vaccine efficacy. We report a strong correlation bAb and nAb responses against the SARS-CoV-2 Omicron (BA ... Full text Link to item Cite

Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial.

Journal Article Nat Med · November 2022 Updated immunization strategies are needed to address multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of the ... Full text Link to item Cite

Complementary antibody lineages achieve neutralization breadth in an HIV-1 infected elite neutralizer.

Journal Article PLoS Pathog · November 2022 Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely difficult to induce by vaccination. Defining the developmental pa ... Full text Link to item Cite

An antibody from single human VH-rearranging mouse neutralizes all SARS-CoV-2 variants through BA.5 by inhibiting membrane fusion.

Journal Article Sci Immunol · October 28, 2022 SARS-CoV-2 Omicron subvariants have generated a worldwide health crisis due to resistance to most approved SARS-CoV-2 neutralizing antibodies and evasion of vaccination-induced antibodies. To manage Omicron subvariants and prepare for new ones, additional ... Full text Link to item Cite

Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine.

Journal Article Nat Commun · October 23, 2022 Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced ... Full text Open Access Link to item Cite

Neutralizing Antibody Activity to Severe Acute Respiratory Syndrome Coronavirus 2 Delta (B.1.617.2) and Omicron (B.1.1.529) After 1 or 2 Doses of BNT162b2 Vaccine in Infection-Naive and Previously Infected Individuals.

Journal Article J Infect Dis · October 17, 2022 Previous reports demonstrated that severe acute respiratory syndrome coronavirus (SARS-CoV-2) binding immunoglobulin G levels did not increase significantly between the first and second doses of the BNT162b2 vaccine in previously infected individuals. We t ... Full text Link to item Cite

A Bivalent Omicron-Containing Booster Vaccine against Covid-19.

Journal Article N Engl J Med · October 6, 2022 BACKGROUND: The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known. METHODS: In this ongoing, phase 2-3 study, we compared the 50-μg bivalent vaccine mRNA-1273.214 (25 μg each of ancestral Wuhan-Hu-1 an ... Full text Link to item Cite

Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection.

Journal Article Sci Transl Med · September 7, 2022 A successful HIV-1 vaccine will require induction of a polyclonal neutralizing antibody (nAb) response, yet vaccine-mediated induction of such a response in primates remains a challenge. We found that a stabilized HIV-1 CH505 envelope (Env) trimer formulat ... Full text Open Access Link to item Cite

Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition.

Journal Article Nat Med · September 2022 The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralizatio ... Full text Link to item Cite

Long-primed germinal centres with enduring affinity maturation and clonal migration.

Journal Article Nature · September 2022 Germinal centres are the engines of antibody evolution. Here, using human immunodeficiency virus (HIV) Env protein immunogen priming in rhesus monkeys followed by a long period without further immunization, we demonstrate germinal centre B (BGC) cells that ... Full text Link to item Cite

Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein.

Journal Article Nat Commun · August 3, 2022 A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2 ... Full text Link to item Cite

Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant.

Journal Article Cell Rep Med · July 19, 2022 The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durabi ... Full text Link to item Cite

Exposure modality influences viral kinetics but not respiratory outcome of COVID-19 in multiple nonhuman primate species.

Journal Article PLoS Pathog · July 2022 The novel coronavirus SARS-CoV-2 emerged in late 2019, rapidly reached pandemic status, and has maintained global ubiquity through the emergence of variants of concern. Efforts to develop animal models have mostly fallen short of recapitulating severe dise ... Full text Link to item Cite

Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike.

Journal Article Cell Rep · June 28, 2022 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sub-lineage has gained in proportion relative to BA.1. Because spike (S) protein variations may underlie differences in their pathobiology, here we determine cryoelectron microsc ... Full text Link to item Cite

Erratum: Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1.

Journal Article Mol Ther Methods Clin Dev · June 9, 2022 [This corrects the article DOI: 10.1016/j.omtm.2019.06.003.]. ... Full text Link to item Cite

Structural diversity of the SARS-CoV-2 Omicron spike.

Journal Article Mol Cell · June 2, 2022 Aided by extensive spike protein mutation, the SARS-CoV-2 Omicron variant overtook the previously dominant Delta variant. Spike conformation plays an essential role in SARS-CoV-2 evolution via changes in receptor-binding domain (RBD) and neutralizing antib ... Full text Link to item Cite

Vertical HIV-1 Transmission in the Setting of Maternal Broad and Potent Antibody Responses.

Journal Article Journal of virology · June 2022 Despite the worldwide availability of antiretroviral therapy (ART), approximately 150,000 pediatric HIV infections continue to occur annually. ART can dramatically reduce HIV mother-to-child transmission (MTCT), but inconsistent drug access and adherence, ... Full text Cite

Broad coverage of neutralization-resistant SIV strains by second-generation SIV-specific antibodies targeting the region involved in binding CD4.

Journal Article PLoS Pathog · June 2022 Both SIV and SHIV are powerful tools for evaluating antibody-mediated prevention and treatment of HIV-1. However, owing to a lack of rhesus-derived SIV broadly neutralizing antibodies (bnAbs), testing of bnAbs for HIV-1 prevention or treatment has thus far ... Full text Link to item Cite

Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody.

Journal Article Cell Rep Med · May 17, 2022 Human immunodeficiency virus type 1 (HIV-1) vaccination of cows has elicited broadly neutralizing antibodies (bNAbs). In this study, monoclonal antibodies (mAbs) are isolated from a clade A (KNH1144 and BG505) vaccinated cow using a heterologous clade B an ... Full text Link to item Cite

Frequent Development of Broadly Neutralizing Antibodies in Early Life in a Large Cohort of Children With Human Immunodeficiency Virus.

Journal Article J Infect Dis · May 16, 2022 BACKGROUND: Recent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after human immunodeficiency virus (HIV) infection compared to adults. METHODS: We evaluated plasma from 212 antiretroviral therapy-naive ... Full text Link to item Cite

Characterization of a vaccine-elicited human antibody with sequence homology to VRC01-class antibodies that binds the C1C2 gp120 domain.

Journal Article Sci Adv · May 6, 2022 Broadly HIV-1-neutralizing VRC01-class antibodies bind the CD4-binding site of Env and contain VH1-2*02-derived heavy chains paired with light chains expressing five-amino acid-long CDRL3s. Their unmutated germline forms do not recognize HIV-1 Env, and the ... Full text Link to item Cite

Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial.

Journal Article Nat Med · May 2022 Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we repor ... Full text Link to item Cite

Defining the risk of SARS-CoV-2 variants on immune protection.

Journal Article Nature · May 2022 The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 ... Full text Link to item Cite

Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers.

Journal Article NPJ Vaccines · April 21, 2022 Integrase Defective Lentiviral Vectors (IDLVs) represent an attractive vaccine platform for delivering HIV-1 antigens, given their ability to induce specific and persistent immune responses in both mice and non-human primates (NHPs). Recent advances in HIV ... Full text Link to item Cite

Homologous and Heterologous Covid-19 Booster Vaccinations.

Journal Article N Engl J Med · March 17, 2022 BACKGROUND: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homolo ... Full text Link to item Cite

mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.

Journal Article Cell Rep · March 15, 2022 The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alon ... Full text Link to item Cite

Enhanced immunity after Ad26.COV2.S vaccine breakthrough infection.

Journal Article Cell Rep Med · March 15, 2022 A study by Kitchin, Richardson et al. finds that breakthrough infection with the SARS-CoV-2 Delta variant in Ad26.COV2.S-vaccinated individuals induces strong neutralizing antibody responses against multiple variants, including the Omicron variant. ... Full text Link to item Cite

Stable Latent HIV Infection and Low-level Viremia Despite Treatment With the Broadly Neutralizing Antibody VRC07-523LS and the Latency Reversal Agent Vorinostat.

Journal Article J Infect Dis · March 2, 2022 We tested the combination of a broadly neutralizing HIV antibody with the latency reversal agent vorinostat (VOR). Eight participants received 2 month-long cycles of VRC07-523LS with VOR. Low-level viremia, resting CD4+ T-cell-associated HIV RNA (rca-RNA) ... Full text Link to item Cite

Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies.

Journal Article Cell Rep · March 1, 2022 HIV-1 clade C envelope immunogens that elicit both neutralizing and non-neutralizing V1V2-scaffold-specific antibodies (protective correlates from RV144 human trial) are urgently needed due to the prevalence of this clade in the most impacted regions world ... Full text Link to item Cite

High thermostability improves neutralizing antibody responses induced by native-like HIV-1 envelope trimers.

Journal Article NPJ Vaccines · February 28, 2022 Soluble HIV-1 envelope glycoprotein (Env) immunogens are a prime constituent of candidate vaccines designed to induce broadly neutralizing antibodies. Several lines of evidence suggest that enhancing Env immunogen thermostability can improve neutralizing a ... Full text Link to item Cite

Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine.

Journal Article bioRxiv · February 14, 2022 Coronavirus vaccines that are highly effective against SARS-CoV-2 variants are needed to control the current pandemic. We previously reported a receptor-binding domain (RBD) sortase A-conjugated ferritin nanoparticle (RBD-scNP) vaccine that induced neutral ... Full text Open Access Link to item Cite

E4orf1 Suppresses E1B-Deleted Adenovirus Vaccine-Induced Immune Responses

Journal Article Vaccines · February 1, 2022 As demonstrated by the recent COVID pandemic, vaccines can reduce the burden arising from infectious agents. Adenoviruses (Ads) with deletion of the early region 1B55K (ΔE1B Ad) are currently being explored for use in vaccine delivery. ΔE1B Ads are differe ... Full text Cite

A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.

Journal Article Sci Transl Med · January 26, 2022 Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly ef ... Full text Link to item Cite

Selection of HIV Envelope Strains for Standardized Assessments of Vaccine-Elicited Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies.

Journal Article J Virol · January 26, 2022 Antibody-dependent cellular cytotoxicity (ADCC) has been correlated with reduced risk of human immunodeficiency virus type 1 (HIV-1) infection in several preclinical vaccine trials and in the RV144 clinical trial, indicating that this is a relevant antibod ... Full text Link to item Cite

Towards a population-based threshold of protection for COVID-19 vaccines.

Journal Article Vaccine · January 21, 2022 Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlat ... Full text Link to item Cite

Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.

Journal Article Science · January 7, 2022 In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at the time o ... Full text Link to item Cite

Cooperation Between Systemic and Mucosal Antibodies Induced by Virosomal Vaccines Targeting HIV-1 Env: Protection of Indian Rhesus Macaques Against Low-Dose Intravaginal SHIV Challenges.

Journal Article Front Immunol · 2022 A virosomal vaccine inducing systemic/mucosal anti-HIV-1 gp41 IgG/IgA had previously protected Chinese-origin rhesus macaques (RMs) against vaginal SHIVSF162P3 challenges. Here, we assessed its efficacy in Indian-origin RMs by intramuscular priming/intrana ... Full text Link to item Cite

Early and Long-Term HIV-1 Immunogenicity Induced in Macaques by the Combined Administration of DNA, NYVAC and Env Protein-Based Vaccine Candidates: The AUP512 Study.

Journal Article Front Immunol · 2022 To control HIV infection there is a need for vaccines to induce broad, potent and long-term B and T cell immune responses. With the objective to accelerate and maintain the induction of substantial levels of HIV-1 Env-specific antibodies and, at the same t ... Full text Link to item Cite

Calibration of two validated SARS-CoV-2 pseudovirus neutralization assays for COVID-19 vaccine evaluation.

Journal Article Sci Rep · December 14, 2021 Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudoviru ... Full text Link to item Cite

Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center

Conference npj Vaccines · December 1, 2021 The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed tha ... Full text Cite

Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study.

Journal Article PLoS Med · December 2021 BACKGROUND: People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbiditi ... Full text Link to item Cite

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease.

Journal Article PLoS Pathog · December 2021 The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully r ... Full text Link to item Cite

Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis.

Journal Article Nat Med · November 2021 The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who rec ... Full text Link to item Cite

ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection.

Journal Article PLoS Pathog · November 2021 Despite antibody-dependent cellular cytotoxicity (ADCC) responses being implicated in protection from HIV-1 infection, there is limited evidence that they control virus replication. The high mutability of HIV-1 enables the virus to rapidly adapt, and thus ... Full text Link to item Cite

Broadly neutralizing monoclonal antibodies for HIV prevention.

Journal Article J Int AIDS Soc · November 2021 INTRODUCTION: The last 12 years have seen remarkable progress in the isolation and characterization of at least five different epitope classes of HIV-specific broadly neutralizing antibodies (bnAbs). Detailed analyses of these bnAb lineages, maturation pat ... Full text Link to item Cite

Diverse antiviral IgG effector activities are predicted by unique biophysical antibody features.

Journal Article Retrovirology · October 30, 2021 BACKGROUND: The critical role of antibody Fc-mediated effector functions in immune defense has been widely reported in various viral infections. These effector functions confer cellular responses through engagement with innate immune cells. The precise mec ... Full text Link to item Cite

COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

Journal Article Nat Commun · October 20, 2021 Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the in vivo prophylactic and therapeutic effect of COVA1-18, a ... Full text Link to item Cite

Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M vaccination.

Journal Article Cell Rep Med · September 21, 2021 Recently approved vaccines have shown remarkable efficacy in limiting SARS-CoV-2-associated disease. However, with the variety of vaccines, immunization strategies, and waning antibody titers, defining the correlates of immunity across a spectrum of antibo ... Full text Link to item Cite

Evaluation of Cell-Based and Surrogate SARS-CoV-2 Neutralization Assays.

Journal Article J Clin Microbiol · September 20, 2021 Determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require the development of well-standardized, reproducible antibody assays. This need has led to the emergence of a variety of neutralization ... Full text Link to item Cite

Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates.

Journal Article Science · September 17, 2021 Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 μg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-Co ... Full text Link to item Cite

Calibration of Two Validated SARS-CoV-2 Pseudovirus Neutralization Assays for COVID-19 Vaccine Evaluation.

Journal Article medRxiv · September 14, 2021 Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States Government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudoviru ... Full text Link to item Cite

Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial.

Journal Article medRxiv · August 15, 2021 BACKGROUND: In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. MET ... Full text Link to item Cite

Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.

Journal Article Nat Commun · August 10, 2021 Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP con ... Full text Link to item Cite

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

Journal Article Cell · August 5, 2021 SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SA ... Full text Open Access Link to item Cite

Antibody responses induced by SHIV infection are more focused than those induced by soluble native HIV-1 envelope trimers in non-human primates.

Journal Article PLoS Pathog · August 2021 The development of an effective human immunodeficiency virus (HIV-1) vaccine is a high global health priority. Soluble native-like HIV-1 envelope glycoprotein trimers (Env), including those based on the SOSIP design, have shown promise as vaccine candidate ... Full text Link to item Cite

AIDSVAX protein boost improves breadth and magnitude of vaccine-induced HIV-1 envelope-specific responses after a 7-year rest period.

Journal Article Vaccine · July 30, 2021 BACKGROUND: Eliciting durable humoral immunity with sufficient breadth and magnitude is important for HIV-1 vaccine design. The HVTN 114 vaccine trial evaluated different boost regimens administered after a 7-year rest period in participants previously enr ... Full text Link to item Cite

A yeast expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates.

Journal Article Sci Immunol · July 15, 2021 Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SA ... Full text Link to item Cite

SnapShot: SARS-CoV-2 antibodies.

Journal Article Cell Host Microbe · July 14, 2021 Full text Link to item Cite

A Derivative of the D5 Monoclonal Antibody That Targets the gp41 N-Heptad Repeat of HIV-1 with Broad Tier-2-Neutralizing Activity.

Journal Article J Virol · July 12, 2021 HIV-1 infection is initiated by the viral glycoprotein Env, which, after interaction with cellular coreceptors, adopts a transient conformation known as the prehairpin intermediate (PHI). The N-heptad repeat (NHR) is a highly conserved region of gp41 expos ... Full text Link to item Cite

Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity.

Journal Article Vaccines (Basel) · July 12, 2021 We have constructed bispecific immunoglobulin-like immunoadhesins that bind to both the HIV-envelope glycoproteins: gp120 and gp41. These immunoadhesins have N terminal domains of human CD4 engrafted onto the N-terminus of the heavy chain of human anti-gp4 ... Full text Link to item Cite

Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial.

Journal Article Vaccine · June 29, 2021 A major challenge for HIV vaccine development is to raise anti-envelope antibodies capable of recognizing and neutralizing diverse strains of HIV-1. Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine construct was designed to pres ... Full text Link to item Cite

SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques.

Journal Article Sci Immunol · June 15, 2021 The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age- ... Full text Link to item Cite

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

Journal Article Nature · June 2021 The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displ ... Full text Link to item Cite

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Journal Article Nature · June 2021 Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and ... Full text Open Access Link to item Cite

Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.

Journal Article PLoS Pathog · June 2021 A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccinati ... Full text Link to item Cite

Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Journal Article Cell · May 27, 2021 Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (b ... Full text Open Access Link to item Cite

A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice.

Journal Article bioRxiv · April 28, 2021 SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid preventi ... Full text Link to item Cite

SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines.

Journal Article Cell Host Microbe · April 14, 2021 All current vaccines for COVID-19 utilize ancestral SARS-CoV-2 spike with the goal of generating protective neutralizing antibodies. The recent emergence and rapid spread of several SARS-CoV-2 variants carrying multiple spike mutations raise concerns about ... Full text Link to item Cite

Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates.

Journal Article NPJ Vaccines · April 9, 2021 The development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being teste ... Full text Link to item Cite

The SARS-CoV-2 Spike variant D614G favors an open conformational state.

Journal Article Sci Adv · April 2021 The COVID-19 (coronavirus disease 2019) pandemic underwent a rapid transition with the emergence of a dominant viral variant (from the "D-form" to the "G-form") that carried an amino acid substitution D614G in its "Spike" protein. The G-form is more infect ... Full text Link to item Cite

Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.

Journal Article N Engl J Med · March 18, 2021 BACKGROUND: Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear. METHODS: We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN ... Full text Link to item Cite

Virus Control in Vaccinated Rhesus Macaques Is Associated with Neutralizing and Capturing Antibodies against the SHIV Challenge Virus but Not with V1V2 Vaccine-Induced Anti-V2 Antibodies Alone.

Journal Article J Immunol · March 15, 2021 The role of vaccine-induced anti-V2 Abs was tested in three protection experiments in rhesus macaques. In an experiment using immunogens similar to those in the RV144 vaccine trial (Anti-envelope [Env]), nine rhesus macaques were coimmunized with gp16092TH ... Full text Link to item Cite

The immunological impact of adenovirus early genes on vaccine-induced responses in mice and nonhuman primates.

Journal Article J Virol · March 10, 2021 Adenovirus (Ad) is being explored for use in the prevention and treatment of a variety of infectious diseases and cancers. Ad with a deletion in early region 3 (ΔE3) provokes a stronger immune response than Ad with deletions in early regions 1 and E3 (ΔE1/ ... Full text Link to item Cite

A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs.

Journal Article Immunity · March 9, 2021 A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion s ... Full text Link to item Cite

Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates.

Journal Article iScience · February 19, 2021 The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity ... Full text Link to item Cite

The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.

Journal Article bioRxiv · February 18, 2021 SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of S ... Full text Open Access Link to item Cite

SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys.

Journal Article bioRxiv · February 17, 2021 Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circul ... Full text Open Access Link to item Cite

COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

Journal Article Res Sq · February 15, 2021 One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have ... Full text Link to item Cite

Lipid-based vaccine nanoparticles for induction of humoral immune responses against HIV-1 and SARS-CoV-2.

Journal Article J Control Release · February 10, 2021 The current health crisis of corona virus disease 2019 (COVID-19) highlights the urgent need for vaccine systems that can generate potent and protective immune responses. Protein vaccines are safe, but conventional approaches for protein-based vaccines oft ... Full text Link to item Cite

Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles.

Journal Article NPJ Vaccines · February 9, 2021 The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistan ... Full text Link to item Cite

Cold sensitivity of the SARS-CoV-2 spike ectodomain.

Journal Article Nat Struct Mol Biol · February 2021 The SARS-CoV-2 spike (S) protein, a primary target for COVID-19 vaccine development, presents its receptor binding domain in two conformations, the receptor-accessible 'up' or receptor-inaccessible 'down' states. Here we report that the commonly used stabi ... Full text Link to item Cite

SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines.

Journal Article bioRxiv · January 29, 2021 The SARS-CoV-2 Spike glycoprotein mediates virus entry and is a major target for neutralizing antibodies. All current vaccines are based on the ancestral Spike with the goal of generating a protective neutralizing antibody response. Several novel SARS-CoV- ... Full text Link to item Cite

The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat.

Journal Article Proc Natl Acad Sci U S A · January 19, 2021 The HIV-1 gp41 N-heptad repeat (NHR) region of the prehairpin intermediate, which is transiently exposed during HIV-1 viral membrane fusion, is a validated clinical target in humans and is inhibited by the Food and Drug Administration (FDA)-approved drug e ... Full text Link to item Cite

D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.

Journal Article Cell Host Microbe · January 13, 2021 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralizat ... Full text Link to item Cite

Immunization by exposure to live virus (SIVmne/HIV-2287) during antiretroviral drug prophylaxis may reduce risk of subsequent viral challenge.

Journal Article PLoS One · 2021 RATIONALE/STUDY DESIGN: A major challenge in the development of HIV vaccines is finding immunogens that elicit protection against a broad range of viral strains. Immunity to a narrow range of viral strains may protect infants of HIV-infected women or partn ... Full text Link to item Cite

Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies.

Journal Article Front Cell Infect Microbiol · 2021 SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral adm ... Full text Link to item Cite

Polyclonal Broadly Neutralizing Antibody Activity Characterized by CD4 Binding Site and V3-Glycan Antibodies in a Subset of HIV-1 Virus Controllers.

Journal Article Front Immunol · 2021 Broadly neutralizing antibodies (bNAbs), known to mediate immune control of HIV-1 infection, only develop in a small subset of HIV-1 infected individuals. Despite being traditionally associated with patients with high viral loads, bNAbs have also been obse ... Full text Link to item Cite

Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates.

Journal Article bioRxiv · December 31, 2020 Development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested fo ... Full text Link to item Cite

Priming with DNA Expressing Trimeric HIV V1V2 Alters the Immune Hierarchy Favoring the Development of V2-Specific Antibodies in Rhesus Macaques.

Journal Article J Virol · December 22, 2020 The RV144 vaccine trial revealed a correlation between reduced risk of HIV infection and the level of nonneutralizing-antibody (Ab) responses targeting specific epitopes in the second variable domain (V2) of the HIV gp120 envelope (Env) protein, suggesting ... Full text Link to item Cite

Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers.

Journal Article J Virol · November 23, 2020 The induction of broadly neutralizing antibodies (bNAbs) is a major goal in vaccine research. HIV-1-infected individuals that develop exceptionally strong bNAb responses, termed elite neutralizers, can inform vaccine design by providing blueprints for the ... Full text Link to item Cite

A Prime/Boost Vaccine Regimen Alters the Rectal Microbiome and Impacts Immune Responses and Viremia Control Post-Simian Immunodeficiency Virus Infection in Male and Female Rhesus Macaques.

Journal Article Journal of virology · November 2020 An efficacious human immunodeficiency virus (HIV) vaccine will likely require induction of both mucosal and systemic immune responses. We compared the immunogenicity and protective efficacy of two mucosal/systemic vaccine regimens and investigated their ef ... Full text Cite

Antigenicity and Immunogenicity of HIV-1 Envelope Trimers Complexed to a Small-Molecule Viral Entry Inhibitor.

Journal Article J Virol · October 14, 2020 Small-molecule viral entry inhibitors, such as BMS-626529 (BMS-529), allosterically block CD4 binding to HIV-1 envelope (Env) and inhibit CD4-induced structural changes in Env trimers. Here, we show that the binding of BMS-529 to clade C soluble chimeric g ... Full text Link to item Cite

Improved killing of HIV-infected cells using three neutralizing and non-neutralizing antibodies.

Journal Article J Clin Invest · October 1, 2020 The correlation of HIV-specific antibody-dependent cellular cytotoxicity (ADCC) responses with protection from and delayed progression of HIV-1 infection provides a rationale to leverage ADCC-mediating antibodies for treatment purposes. We evaluated ADCC m ... Full text Link to item Cite

SIV infection duration largely determines broadening of neutralizing antibody response in macaques.

Journal Article J Clin Invest · October 1, 2020 The development of broadly neutralizing antibodies (BNAbs) in HIV infection is a result of long-term coevolutionary interaction between viruses and antibodies. Understanding how this interaction promotes the increase of neutralization breadth during infect ... Full text Link to item Cite

Safety and immunogenicity of two heterologous HIV vaccine regimens in healthy, HIV-uninfected adults (TRAVERSE): a randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study.

Journal Article The lancet. HIV · October 2020 BackgroundBioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared the safety, tolerability, and immunogenicity of a newly developed, tetravalent Ad26 vaccine with the previously tested ... Full text Cite

Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus.

Journal Article Cell · August 20, 2020 A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national ... Full text Link to item Cite

Structural and functional evaluation of de novo-designed, two-component nanoparticle carriers for HIV Env trimer immunogens.

Journal Article PLoS Pathog · August 2020 Two-component, self-assembling nanoparticles represent a versatile platform for multivalent presentation of viral antigens. Computational design of protein nanoparticles with differing sizes and geometries enables combination with antigens of choice to tes ... Full text Link to item Cite

Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates.

Journal Article PLoS Pathog · August 2020 The induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent aut ... Full text Link to item Cite

The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State.

Journal Article bioRxiv · July 26, 2020 The COVID-19 pandemic underwent a rapid transition with the emergence of a SARS-CoV-2 variant that carried the amino acid substitution D614G in the Spike protein that became globally prevalent. The G-form is both more infectious in vitro and associated wit ... Full text Link to item Cite

Robust antibody and cellular responses induced by DNA-only vaccination for HIV.

Journal Article JCI Insight · July 9, 2020 BACKGROUNDHVTN 098, a randomized, double-blind, placebo-controlled trial, evaluated the safety, tolerability, and immunogenicity of PENNVAX-GP HIV DNA vaccine, administered with or without plasmid IL-12 (pIL-12), via intradermal (ID) or intramuscular (IM) ... Full text Link to item Cite

An Engineered Biomimetic MPER Peptide Vaccine Induces Weakly HIV Neutralizing Antibodies in Mice.

Journal Article Ann Biomed Eng · July 2020 A vaccine that induces broadly neutralizing antibodies (bnAbs) against the human immunodeficiency virus (HIV) would be instrumental in controlling the disease. The membrane proximal external region (MPER) peptide is an appealing antigen candidate since it ... Full text Link to item Cite

3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope-specific plasma cells and humoral immunity in nonhuman primates.

Journal Article Sci Immunol · June 19, 2020 A fundamental challenge in vaccinology is learning how to induce durable antibody responses. Live viral vaccines induce antibody responses that last a lifetime, but those induced with subunit vaccines wane rapidly. Studies in mice and humans have establish ... Full text Link to item Cite

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses.

Journal Article Vaccines (Basel) · June 6, 2020 Studies have shown that blockade of CTLA-4 promoted the expansion of germinal center B-cells in viral infection or immunization with model antigens. Few studies have evaluated the immunological consequences of CTLA-4 blockade during immunization against re ... Full text Link to item Cite

T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers.

Journal Article Nat Med · June 2020 Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induc ... Full text Link to item Cite

Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial.

Journal Article PLoS Pathog · June 2020 DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizin ... Full text Link to item Cite

Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge.

Journal Article Cell Rep · May 12, 2020 We compare immunogenicity and protective efficacy of an HIV vaccine comprised of env and gag DNA and Env (Envelope) proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA + protein in contralateral ... Full text Link to item Cite

Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials.

Journal Article PLoS medicine · May 2020 BackgroundDNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with ... Full text Cite

Brief Report: Prediction of Serum HIV-1 Neutralization Titers After Passive Administration of VRC01.

Journal Article J Acquir Immune Defic Syndr · April 1, 2020 BACKGROUND: VRC01 is a human IgG1 broadly neutralizing antibody (bnAb) that binds to the HIV-1 envelope glycoprotein. It is being evaluated in two ongoing Phase 2b trials, the first efficacy assessment of a passively-administered bnAb for HIV-1 prevention. ... Full text Link to item Cite

Optimization and qualification of a functional anti-drug antibody assay for HIV-1 bnAbs.

Journal Article J Immunol Methods · April 2020 The recent identification of human monoclonal antibodies with broad and potent neutralizing activity against HIV-1 (bnAbs) has resulted in substantial efforts to develop these molecules for clinical use in the prevention and treatment of HIV-1 infection. A ... Full text Link to item Cite

Implementation of a three-tiered approach to identify and characterize anti-drug antibodies raised against HIV-specific broadly neutralizing antibodies.

Journal Article J Immunol Methods · April 2020 The ability to detect, quantify, and interrogate the properties of immune responses raised against biological therapeutics is not only important to our understanding of these molecules, but also to their success in the clinic. A tiered assay approach to id ... Full text Link to item Cite

Correction: ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type.

Journal Article PLoS Pathog · April 2020 [This corrects the article DOI: 10.1371/journal.ppat.1008121.]. ... Full text Link to item Cite

The Impact of Sustained Immunization Regimens on the Antibody Response to Oligomannose Glycans.

Journal Article ACS Chem Biol · March 20, 2020 The high mannose patch (HMP) of the HIV envelope protein (Env) is the structure most frequently targeted by broadly neutralizing antibodies; therefore, many researchers have attempted to use mimics of this region as a vaccine immunogen. In our previous eff ... Full text Link to item Cite

Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants.

Journal Article mBio · March 10, 2020 Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope ... Full text Link to item Cite

Engagement of monocytes, NK cells, and CD4+ Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIVmac251 vaginal acquisition.

Journal Article PLoS Pathog · March 2020 The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease the risk of HIV acquisition in humans, with equal effectiveness in both males and females. Similarly, an equivalent SIV-based ALVAC vaccine regimen decre ... Full text Link to item Cite

Neutralizing Antibody Induction by HIV-1 Envelope Glycoprotein SOSIP Trimers on Iron Oxide Nanoparticles May Be Impaired by Mannose Binding Lectin.

Journal Article J Virol · February 28, 2020 We covalently attached human immunodeficiency virus type 1 (HIV-1) Env SOSIP trimers to iron oxide nanoparticles (IO-NPs) to create a particulate immunogen for neutralizing antibody (NAb) induction. The attached trimers, ∼20 per particle, retained native-l ... Full text Link to item Cite

Expression of CD40L by the ALVAC-Simian Immunodeficiency Virus Vector Abrogates T Cell Responses in Macaques.

Journal Article J Virol · February 28, 2020 Immunization with recombinant ALVAC/gp120 alum vaccine provided modest protection from human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) acquisition in humans and macaques. Vaccine-mediated protection was associated with t ... Full text Link to item Cite

Immune checkpoint modulation enhances HIV-1 antibody induction.

Journal Article Nat Commun · February 19, 2020 Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immun ... Full text Open Access Link to item Cite

Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles following HIV Envelope Immunization.

Journal Article Cell Rep · February 4, 2020 HIV-1-infected infants develop broadly neutralizing antibodies (bnAbs) more rapidly than adults, suggesting differences in the neonatal versus adult responses to the HIV-1 envelope (Env). Here, trimeric forms of HIV-1 Env immunogens elicit increased gp120- ... Full text Open Access Link to item Cite

In vivo delivery of synthetic DNA-encoded antibodies induces broad HIV-1-neutralizing activity.

Journal Article J Clin Invest · February 3, 2020 Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous broadly neutralizing HIV-1 monoclonal antibodies (bNAbs) have been developed that possess the characteristics necessary for potenti ... Full text Link to item Cite

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines.

Journal Article PLoS Med · February 2020 BACKGROUND: HVTN 100 evaluated the safety and immunogenicity of an HIV subtype C pox-protein vaccine regimen, investigating a 12-month booster to extend vaccine-induced immune responses. METHODS AND FINDINGS: A phase 1-2 randomized double-blind placebo-con ... Full text Link to item Cite

Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency.

Journal Article J Virol · January 31, 2020 Induction of protective antibodies is a critical goal of HIV-1 vaccine development. One strategy is to induce nonneutralizing antibodies (NNAbs) that kill virus-infected cells, as these antibody specificities have been implicated in slowing HIV-1 disease p ... Full text Link to item Cite

HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions.

Journal Article JCI Insight · January 30, 2020 In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent ... Full text Link to item Cite

Effect of HIV Envelope Vaccination on the Subsequent Antibody Response to HIV Infection.

Journal Article mSphere · January 29, 2020 Analysis of breakthrough HIV-1 infections could elucidate whether prior vaccination primes relevant immune responses. Here, we measured HIV-specific antibody responses in 14 South African volunteers who acquired HIV infection after participating in phase 1 ... Full text Link to item Cite

Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector.

Journal Article Sci Rep · December 27, 2019 Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 imm ... Full text Link to item Cite

Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.

Journal Article Science · December 6, 2019 INTRODUCTION: A major goal of HIV-1 vaccine development is the design of immunogens that induce broadly neutralizing antibodies (bnAbs). However, vaccination of humans has not resulted in the induction of affinity-matured and potent HIV-1 bnAbs. To devise ... Full text Link to item Cite

Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.

Journal Article Cell Rep · December 3, 2019 Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-2∗02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but ... Full text Link to item Cite

Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence

Conference Nature Communications · December 1, 2019 Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we g ... Full text Cite

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type.

Journal Article PLoS Pathog · December 2019 The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of A ... Full text Link to item Cite

Cooperation between somatic mutation and germline-encoded residues enables antibody recognition of HIV-1 envelope glycans.

Journal Article PLoS Pathog · December 2019 Viral glycoproteins are a primary target for host antibody responses. However, glycans on viral glycoproteins can hinder antibody recognition since they are self glycans derived from the host biosynthesis pathway. During natural HIV-1 infection, neutralizi ... Full text Link to item Cite

Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01.

Journal Article Cell Host Microbe · November 13, 2019 Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. He ... Full text Link to item Cite

DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial.

Journal Article J Clin Invest · November 1, 2019 BACKGROUNDRV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of reg ... Full text Link to item Cite

Safety and immunogenicity of a multivalent HIV vaccine comprising envelope protein with either DNA or NYVAC vectors (HVTN 096): a phase 1b, double-blind, placebo-controlled trial.

Journal Article Lancet HIV · November 2019 BACKGROUND: Up to now, immunisation regimens that have been assessed for development of HIV vaccines have included purified envelope (Env) protein among the boosting components of the regimen. We postulated that co-administration of Env protein with either ... Full text Link to item Cite

Human Immunodeficiency Virus C.1086 Envelope gp140 Protein Boosts following DNA/Modified Vaccinia Virus Ankara Vaccination Fail To Enhance Heterologous Anti-V1V2 Antibody Response and Protection against Clade C Simian-Human Immunodeficiency Virus Challenge.

Journal Article J Virol · October 15, 2019 The RV144 human immunodeficiency virus type 1 (HIV-1) vaccine trial showed a strong association between anti-gp70 V1V2 scaffold (V1V2) and anti-V2 hot spot peptide (V2 HS) antibody responses and reduced risk of HIV infection. Accordingly, a primary goal fo ... Full text Link to item Cite

Antibody Responses Elicited by Immunization with BG505 Trimer Immune Complexes.

Journal Article J Virol · October 15, 2019 Immune complex (IC) vaccines have been successfully used to increase immune responses against various pathogens, including HIV-1. Additionally, IC vaccines can induce qualitatively different antibody responses, with distinct antigenic specificities compare ... Full text Link to item Cite

Isolation and Structure of an Antibody that Fully Neutralizes Isolate SIVmac239 Reveals Functional Similarity of SIV and HIV Glycan Shields.

Journal Article Immunity · October 15, 2019 HIV- and SIV-envelope (Env) trimers are both extensively glycosylated, and antibodies identified to date have been unable to fully neutralize SIVmac239. Here, we report the isolation, structure, and glycan interactions of antibody ITS90.03, a monoclonal an ... Full text Link to item Cite

Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle.

Journal Article Nat Commun · September 19, 2019 The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in ... Full text Link to item Cite

Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa.

Journal Article Sci Transl Med · September 18, 2019 One of the most successful HIV vaccines to date, the RV144 vaccine tested in Thailand, demonstrated correlates of protection including cross-clade V1V2 immunoglobulin G (IgG) breadth, Env-specific CD4+ T cell polyfunctionality, and antibody-dependent cellu ... Full text Link to item Cite

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1.

Journal Article Mol Ther Methods Clin Dev · September 13, 2019 The aim of this work was to start collecting information on rational combination of antibody (Ab) and T cell vaccines into single regimens. Two promising candidate HIV-1 vaccine strategies, sequential isolates of CH505 virus Envs developed for initiation o ... Full text Link to item Cite

Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.

Journal Article PLoS Pathog · September 2019 The CD4 binding site (CD4bs) of the HIV-1 envelope glycoprotein is susceptible to multiple lineages of broadly neutralizing antibodies (bnAbs) that are attractive to elicit with vaccines. The CH235 lineage (VH1-46) of CD4bs bnAbs is particularly attractive ... Full text Link to item Cite

Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen.

Journal Article J Virol · July 15, 2019 The benefits of mucosal vaccines over injected vaccines are difficult to ascertain, since mucosally administered vaccines often induce serum antibody responses of lower magnitude than those induced by injected vaccines. This study aimed to determine if muc ... Full text Link to item Cite

Difficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations.

Journal Article Nat Commun · July 1, 2019 The HIV-1 envelope (Env) is the target for neutralizing antibodies and exists on the surface of virions in open or closed conformations. Difficult-to-neutralize viruses (tier 2) express Env in a closed conformation antigenic for broadly neutralizing antibo ... Full text Link to item Cite

Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.

Journal Article Nature · June 2019 Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological re ... Full text Cite

Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence.

Journal Article Nat Commun · May 29, 2019 Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we g ... Full text Link to item Cite

A Single Substitution in gp41 Modulates the Neutralization Profile of SHIV during In Vivo Adaptation.

Journal Article Cell Rep · May 28, 2019 The HIV-1 envelope glycoprotein (Env) maintains a delicate balance between mediating viral entry and escaping antibody neutralization. Adaptation during transmission of neutralization-sensitive Envs with an "open" conformation remains poorly understood. By ... Full text Link to item Cite

Bridging Vaccine-Induced HIV-1 Neutralizing and Effector Antibody Responses in Rabbit and Rhesus Macaque Animal Models.

Journal Article J Virol · May 15, 2019 Studies in animal models are essential prerequisites for clinical trials of candidate HIV vaccines. Small animals, such as rabbits, are used to evaluate promising strategies prior to further immunogenicity and efficacy testing in nonhuman primates. Our goa ... Full text Link to item Cite

Rapid Boosting of HIV-1 Neutralizing Antibody Responses in Humans Following a Prolonged Immunologic Rest Period.

Journal Article J Infect Dis · May 5, 2019 BACKGROUND: The durability and breadth of human immunodeficiency virus type 1 (HIV-1)-specific immune responses elicited through vaccination are important considerations in the development of an effective HIV-1 vaccine. Responses to HIV-1 envelope subunit ... Full text Link to item Cite

Antibody Fab-Fc properties outperform titer in predictive models of SIV vaccine-induced protection.

Journal Article Mol Syst Biol · May 2, 2019 Characterizing the antigen-binding and innate immune-recruiting properties of the humoral response offers the chance to obtain deeper insights into mechanisms of protection than revealed by measuring only overall antibody titer. Here, a high-throughput, mu ... Full text Link to item Cite

Adaptation of an R5 Simian-Human Immunodeficiency Virus Encoding an HIV Clade A Envelope with or without Ablation of Adaptive Host Immunity: Differential Selection of Viral Mutants.

Journal Article J Virol · May 1, 2019 Simian-human immunodeficiency virus (SHIV) infection in rhesus macaques (RMs) resembles human immunodeficiency virus type 1 (HIV-1) infection in humans and serves as a tool to evaluate candidate AIDS vaccines. HIV-1 clade A (HIV-A) predominates in parts of ... Full text Link to item Cite

Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques.

Journal Article Mol Ther Nucleic Acids · April 15, 2019 Despite the enormous effort in the development of effective vaccines against HIV-1, no vaccine candidate has elicited broadly neutralizing antibodies in humans. Thus, generation of more effective anti-HIV vaccines is critically needed. Here we characterize ... Full text Link to item Cite

Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in Women Chronically Infected with HIV-1.

Journal Article J Virol · April 1, 2019 The humoral response to invading mucosal pathogens comprises multiple antibody isotypes derived from systemic and mucosal compartments. To understand the contribution of each antibody isotype/source to the mucosal humoral response, parallel investigation o ... Full text Link to item Cite

Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: a phase 1 randomised controlled trial.

Journal Article Lancet HIV · April 2019 BACKGROUND: A preventive vaccine for HIV is a crucial public health need; adeno-associated virus (AAV)-mediated antibody gene delivery could be an alternative to immunisation to induce sustained expression of neutralising antibodies to prevent HIV. We asse ... Full text Link to item Cite

Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.

Journal Article PLoS Comput Biol · April 2019 The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials. A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficac ... Full text Link to item Cite

Correction: HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.

Journal Article PLoS Pathog · March 2019 [This corrects the article DOI: 10.1371/journal.ppat.1007431.]. ... Full text Link to item Cite

Oligomannose Glycopeptide Conjugates Elicit Antibodies Targeting the Glycan Core Rather than Its Extremities.

Journal Article ACS Cent Sci · February 27, 2019 Up to ∼20% of HIV-infected individuals eventually develop broadly neutralizing antibodies (bnAbs), and many of these antibodies (∼40%) target a region of dense high-mannose glycosylation on gp120 of the HIV envelope protein, known as the "high-mannose patc ... Full text Link to item Cite

Vaccine induction of antibodies and tissue-resident CD8+ T cells enhances protection against mucosal SHIV-infection in young macaques.

Journal Article JCI Insight · February 21, 2019 Antibodies and cytotoxic T cells represent 2 arms of host defense against pathogens. We hypothesized that vaccines that induce both high-magnitude CD8+ T cell responses and antibody responses might confer enhanced protection against HIV. To test this hypot ... Full text Link to item Cite

HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge.

Journal Article Nat Commun · February 18, 2019 The oral mucosa is an attractive site for mucosal vaccination, however the thick squamous epithelium limits antigen uptake. Here we utilize a modified needle-free injector to deliver immunizations to the sublingual and buccal (SL/B) tissue of rhesus macaqu ... Full text Link to item Cite

Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.

Journal Article J Virol · February 15, 2019 In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals. The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have be ... Full text Link to item Cite

Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector.

Journal Article Viruses · February 15, 2019 A chimeric vesicular stomatitis virus with the glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, is a potent viral vaccine vector that overcomes several of the limitations of wild-type VSV. Here, we evaluated the potential of VSV-GP as an HIV ... Full text Link to item Cite

Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost.

Conference J Virol · February 1, 2019 The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different pox ... Full text Link to item Cite

Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC.

Journal Article J Virol · February 1, 2019 As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competen ... Full text Link to item Cite

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.

Journal Article Cell Host Microbe · January 9, 2019 Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large vir ... Full text Link to item Cite

Introduction of the YTE mutation into the non-immunogenic HIV bnAb PGT121 induces anti-drug antibodies in macaques.

Journal Article PLoS One · 2019 Recombinant antibodies play increasingly important roles as immunotherapeutic treatments for human cancers as well as inflammatory and infectious diseases and have revolutionized their management. In addition, their therapeutic potential may be enhanced by ... Full text Link to item Cite

Antibody-Dependent Cellular Cytotoxicity (ADCC)-Mediating Antibodies Constrain Neutralizing Antibody Escape Pathway.

Journal Article Front Immunol · 2019 Both neutralization and antibody-dependent cellular cytotoxicity (ADCC) may be required for effective protection against HIV-1 infection. While there is extensive information on the targets of early neutralizing antibody (nAb) responses, much less is known ... Full text Link to item Cite

Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier.

Journal Article Immunity · December 18, 2018 Elicitation of VRC01-class broadly neutralizing antibodies (bnAbs) is an appealing approach for a preventative HIV-1 vaccine. Despite extensive investigations, strategies to induce VRC01-class bnAbs and overcome the barrier posed by the envelope N276 glyca ... Full text Link to item Cite

Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition.

Journal Article J Med Chem · November 21, 2018 The N332 high-mannose glycan on the HIV-1 gp120 V3-loop is the target of many bNAbs. About 17% HIV isolates carry the N332 to N334 mutation, but the antibody recognition of the N334 N-glycan and its immunogenicity are not well characterized. Here we report ... Full text Link to item Cite

Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys.

Journal Article Mucosal Immunol · November 2018 Breast milk HIV-1 transmission is currently the predominant contributor to pediatric HIV infections. Yet, only ~10% of breastfeeding infants born to untreated HIV-infected mothers become infected. This study assessed the protective capacity of natural HIV ... Full text Link to item Cite

HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.

Journal Article PLoS Pathog · November 2018 Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination. VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because ... Full text Link to item Cite

Design, display and immunogenicity of HIV1 gp120 fragment immunogens on virus-like particles.

Journal Article Vaccine · October 8, 2018 The broadly neutralizing antibody against HIV-1, b12, binds to the CD4 binding site (CD4bs) on the outer domain (OD) of the gp120 subunit of HIV-1 Env. We have previously reported the design of an E. coli expressed fragment of HIV-1 gp120, b122a, containin ... Full text Link to item Cite

Characterization of the Transmitted Virus in an Ongoing HIV-1 Epidemic Driven by Injecting Drug Use.

Journal Article AIDS Res Hum Retroviruses · October 2018 Understanding features of the HIV-1 transmission process has the potential to inform biological interventions for prevention. We have examined the transmitted virus in a cohort of people who inject drugs and who are at risk of HIV-1 infection through blood ... Full text Link to item Cite

Germline-targeting and Reverse Engineering to Elicit CH235.12 Lineage bNAbs

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2018 Link to item Cite

Bridging Vaccine-induced Antibody Responses in Rabbit and Rhesus Macaque Animal Models

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2018 Link to item Cite

Bacterially expressed HIV-1 gp120 outer-domain fragment immunogens with improved stability and affinity for CD4-binding site neutralizing antibodies.

Journal Article J Biol Chem · September 28, 2018 Protein minimization is an attractive approach for designing vaccines against rapidly evolving pathogens such as human immunodeficiency virus, type 1 (HIV-1), because it can help in focusing the immune response toward conserved conformational epitopes pres ... Full text Link to item Cite

Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques.

Journal Article J Virol · August 1, 2018 We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. ... Full text Link to item Cite

Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19).

Journal Article Lancet · July 21, 2018 BACKGROUND: More than 1·8 million new cases of HIV-1 infection were diagnosed worldwide in 2016. No licensed prophylactic HIV-1 vaccine exists. A major limitation to date has been the lack of direct comparability between clinical trials and preclinical stu ... Full text Link to item Cite

Novel Strategy To Adapt Simian-Human Immunodeficiency Virus E1 Carrying env from an RV144 Volunteer to Rhesus Macaques: Coreceptor Switch and Final Recovery of a Pathogenic Virus with Exclusive R5 Tropism.

Journal Article J Virol · July 15, 2018 The phase III RV144 human immunodeficiency virus (HIV) vaccine trial conducted in Thailand remains the only study to show efficacy in decreasing the HIV acquisition risk. In Thailand, circulating recombinant forms of HIV clade A/E (CRF01_AE) predominate; i ... Full text Link to item Cite

Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial.

Journal Article Lancet HIV · July 2018 BACKGROUND: Modest efficacy was reported for the HIV vaccine tested in the RV144 trial, which comprised a canarypox vector (ALVAC) and envelope (env) glycoprotein (gp120). These vaccine components were adapted to express HIV-1 antigens from strains circula ... Full text Link to item Cite

Modified Newcastle Disease virus as an improved vaccine vector against Simian Immunodeficiency virus.

Journal Article Sci Rep · June 12, 2018 SIV infection in macaques is a relevant animal model for HIV pathogenesis and vaccine study in humans. To design a safe and effective vaccine against HIV, we evaluated the suitability of naturally-occurring avirulent Newcastle disease virus (NDV) strains a ... Full text Link to item Cite

Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.

Journal Article J Exp Med · June 4, 2018 T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside ... Full text Link to item Cite

HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition.

Journal Article Nat Med · June 2018 Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)-SIV, DNA-SIV and Ad26-SI ... Full text Link to item Cite

Multivalent Antigen Presentation Enhances the Immunogenicity of a Synthetic Three-Component HIV-1 V3 Glycopeptide Vaccine.

Journal Article ACS Cent Sci · May 23, 2018 HIV-1 envelope glycoproteins gp120 and gp41 are presented on the virus surface as a trimer of heterodimer and are the targets of broadly neutralizing antibodies (bNAbs). We describe here the synthesis and preliminary immunological evaluation of a three-com ... Full text Link to item Cite

Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection.

Journal Article Nat Commun · May 15, 2018 Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in ... Full text Link to item Cite

Structural and immunologic correlates of chemically stabilized HIV-1 envelope glycoproteins.

Journal Article PLoS Pathog · May 2018 Inducing broad spectrum neutralizing antibodies against challenging pathogens such as HIV-1 is a major vaccine design goal, but may be hindered by conformational instability within viral envelope glycoproteins (Env). Chemical cross-linking is widely used f ... Full text Link to item Cite

Immunogenicity in Rabbits of HIV-1 SOSIP Trimers from Clades A, B, and C, Given Individually, Sequentially, or in Combination.

Journal Article J Virol · April 15, 2018 Recombinant soluble HIV-1 envelope glycoprotein (Env) SOSIP trimers are a design platform for inducing broadly neutralizing antibodies (bNAbs) by vaccination. To date, these and alternative designs of native-like trimers, given singly or in pairs, have not ... Full text Link to item Cite

Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates.

Journal Article J Virol · April 15, 2018 A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In ... Full text Link to item Cite

HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees.

Journal Article J Virol · April 15, 2018 Induction of broadly cross-reactive antiviral humoral responses with the capacity to target globally diverse circulating strains is a key goal for HIV-1 immunogen design. A major gap in the field is the identification of diverse HIV-1 envelope antigens to ... Full text Open Access Link to item Cite

HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis.

Journal Article J Virol · April 1, 2018 Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human imm ... Full text Link to item Cite

Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma.

Journal Article PLoS Pathog · April 2018 Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccin ... Full text Link to item Cite

Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial.

Journal Article J Infect Dis · March 28, 2018 BACKGROUND: HVTN 505 was a human immunodeficiency virus type 1 (HIV-1) preventive vaccine efficacy trial of a DNA/recombinant adenovirus serotype 5 (rAd5) vaccine regimen. We assessed antibody responses measured 1 month after final vaccination (month 7) as ... Full text Link to item Cite

A Trimeric HIV-1 Envelope gp120 Immunogen Induces Potent and Broad Anti-V1V2 Loop Antibodies against HIV-1 in Rabbits and Rhesus Macaques.

Journal Article J Virol · March 1, 2018 Trimeric HIV-1 envelope (Env) immunogens are attractive due to their ability to display quaternary epitopes targeted by broadly neutralizing antibodies (bNAbs) while obscuring unfavorable epitopes. Results from the RV144 trial highlighted the importance of ... Full text Link to item Cite

Neutralization tiers of HIV-1.

Journal Article Curr Opin HIV AIDS · March 2018 PURPOSE OF REVIEW: HIV-1 isolates are often classified on the basis of neutralization 'tier' phenotype. Tier classification has important implications for the monitoring and interpretation of vaccine-elicited neutralizing antibody responses. The molecular ... Full text Link to item Cite

Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

Journal Article J Virol · March 1, 2018 Recently discovered broadly neutralizing antibodies (bNAbs) against HIV-1 demonstrate extensive breadth and potency against diverse HIV-1 strains and represent a promising approach for the treatment and prevention of HIV-1 infection. The breadth and potenc ... Full text Link to item Cite

Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections.

Journal Article PLoS Pathog · March 2018 There is great interest in passive transfer of broadly neutralizing antibodies (bnAbs) and engineered bispecific antibodies (Abs) for prevention of HIV-1 infections due to their in vitro neutralization breadth and potency against global isolates and long i ... Full text Link to item Cite

Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers.

Journal Article J Biol Chem · February 2, 2018 To provide protective immunity against circulating primary HIV-1 strains, a vaccine most likely has to induce broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) spike. Recombinant Env trimers such as the prototype BG505 SOSIP.664 that ... Full text Link to item Cite

Epitopes for neutralizing antibodies induced by HIV-1 envelope glycoprotein BG505 SOSIP trimers in rabbits and macaques.

Journal Article PLoS Pathog · February 2018 The native-like, soluble SOSIP.664 trimer based on the BG505 clade A env gene of HIV-1 is immunogenic in various animal species, of which the most studied are rabbits and rhesus macaques. The trimer induces autologous neutralizing antibodies (NAbs) consist ... Full text Link to item Cite

A single, continuous metric to define tiered serum neutralization potency against HIV.

Journal Article Elife · January 19, 2018 HIV-1 Envelope (Env) variants are grouped into tiers by their neutralization-sensitivity phenotype. This helped to recognize that tier 1 neutralization responses can be elicited readily, but do not protect against new infections. Tier 3 viruses are the lea ... Full text Link to item Cite

Combination Adenovirus and Protein Vaccines Prevent Infection or Reduce Viral Burden after Heterologous Clade C Simian-Human Immunodeficiency Virus Mucosal Challenge.

Journal Article J Virol · January 15, 2018 HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of adenovirus (Ad) vectors expressing HIV 1086.C (clade C) envelope glycoprotein (Env), SIV Gag p55, and human pegiv ... Full text Link to item Cite

Increased surface expression of HIV-1 envelope is associated with improved antibody response in vaccinia prime/protein boost immunization.

Journal Article Virology · January 15, 2018 HIV-1 envelope (Env)-based vaccines have so far largely failed to induce antibodies that prevent HIV-1 infection. One factor proposed to limit the immunogenicity of cell-associated Env is its low level of expression on the cell surface, restricting accessi ... Full text Link to item Cite

Validation of an automated system for aliquoting of HIV-1 Env-pseudotyped virus stocks.

Journal Article PLoS One · 2018 The standardized assessments of HIV-specific immune responses are of main interest in the preclinical and clinical stage of HIV-1 vaccine development. In this regard, HIV-1 Env-pseudotyped viruses play a central role for the evaluation of neutralizing anti ... Full text Link to item Cite

Generation and characterization of a bivalent protein boost for future clinical trials: HIV-1 subtypes CR01_AE and B gp120 antigens with a potent adjuvant.

Journal Article PLoS One · 2018 The RV144 Phase III clinical trial with ALVAC-HIV prime and AIDSVAX B/E subtypes CRF01_AE (A244) and B (MN) gp120 boost vaccine regime in Thailand provided a foundation for the future development of improved vaccine strategies that may afford protection ag ... Full text Link to item Cite

IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells.

Journal Article Commun Biol · 2018 HIV continues to be a major global health issue. In spite of successful prevention interventions and treatment methods, the development of an HIV vaccine remains a major priority for the field and would be the optimal strategy to prevent new infections. We ... Full text Open Access Link to item Cite

Increased breadth of HIV-1 neutralization achieved by diverse antibody clones each with limited neutralization breadth.

Journal Article PLoS One · 2018 Broadly neutralizing antibodies (bNAbs) are rarely elicited by current human immunodeficiency virus type 1 (HIV-1) vaccine designs, but the presence of bNAbs in naturally infected individuals may be associated with high plasma viral loads, suggesting that ... Full text Link to item Cite

Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.

Journal Article Cell Rep · December 26, 2017 The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma ant ... Full text Link to item Cite

Synthetic Three-Component HIV-1 V3 Glycopeptide Immunogens Induce Glycan-Dependent Antibody Responses.

Journal Article Cell Chem Biol · December 21, 2017 Eliciting broadly neutralizing antibody (bNAb) responses against HIV-1 is a major goal for a prophylactic HIV-1 vaccine. One approach is to design immunogens based on known broadly neutralizing epitopes. Here we report the design and synthesis of an HIV-1 ... Full text Link to item Cite

HIV-1 gp120 and Modified Vaccinia Virus Ankara (MVA) gp140 Boost Immunogens Increase Immunogenicity of a DNA/MVA HIV-1 Vaccine.

Journal Article J Virol · December 15, 2017 An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia virus Ankara (MVA) ex ... Full text Link to item Cite

Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.

Journal Article Hum Vaccin Immunother · December 2, 2017 Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subt ... Full text Link to item Cite

Pathogenic Correlates of Simian Immunodeficiency Virus-Associated B Cell Dysfunction.

Journal Article J Virol · December 1, 2017 We compared and contrasted pathogenic (in pig-tailed macaques [PTMs]) and nonpathogenic (in African green monkeys [AGMs]) SIVsab infections to assess the significance of the B cell dysfunction observed in simian (SIV) and human immunodeficiency virus (HIV) ... Full text Link to item Cite

Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.

Journal Article Nat Commun · November 23, 2017 A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4- ... Full text Open Access Link to item Cite

Exploration of broadly neutralizing antibody fragments produced in bacteria for the control of HIV.

Journal Article Hum Vaccin Immunother · November 2, 2017 While broadly neutralizing antibodies (bnAbs) are a promising preventative and therapeutic tool for HIV infection, production is difficult and expensive. Production of antibody-like fragments in bacterial cytoplasm provides a cheaper alternative. This work ... Full text Link to item Cite

HIV DNA-Adenovirus Multiclade Envelope Vaccine Induces gp41 Antibody Immunodominance in Rhesus Macaques.

Journal Article J Virol · November 1, 2017 Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 an ... Full text Link to item Cite

Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial.

Journal Article PLoS Med · November 2017 BACKGROUND: VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhu ... Full text Link to item Cite

Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics and Specificities of Antibody Responses against HIV-1 Env in Macaques.

Journal Article J Virol · October 1, 2017 Evaluation of the epitope specificities, locations (systemic or mucosal), and effector functions of antibodies elicited by novel HIV-1 immunogens engineered to improve exposure of specific epitopes is critical for HIV-1 vaccine development. Utilizing an ar ... Full text Link to item Cite

Increased, Durable B-Cell and ADCC Responses Associated with T-Helper Cell Responses to HIV-1 Envelope in Macaques Vaccinated with gp140 Occluded at the CD4 Receptor Binding Site.

Journal Article J Virol · October 1, 2017 Strategies are needed to improve the immunogenicity of HIV-1 envelope (Env) antigens (Ag) for more long-lived, efficacious HIV-1 vaccine-induced B-cell responses. HIV-1 Env gp140 (native or uncleaved molecules) or gp120 monomeric proteins elicit relatively ... Full text Link to item Cite

Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments.

Journal Article J Virol · October 1, 2017 In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studi ... Full text Link to item Cite

A single gp120 residue can affect HIV-1 tropism in macaques.

Journal Article PLoS Pathog · September 2017 Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including ... Full text Link to item Cite

Correction: Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization.

Journal Article PLoS Pathog · September 2017 [This corrects the article DOI: 10.1371/journal.ppat.1005742.]. ... Full text Link to item Cite

Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization.

Journal Article Cell Rep · August 22, 2017 The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of na ... Full text Link to item Cite

Partial efficacy of a broadly neutralizing antibody against cell-associated SHIV infection.

Journal Article Sci Transl Med · August 9, 2017 Broadly neutralizing antibodies (BnAbs) protect macaques from cell-free simian/human immunodeficiency virus (SHIV) challenge, but their efficacy against cell-associated SHIV is unclear. Virus in cell-associated format is highly infectious, present in trans ... Full text Link to item Cite

HIV-1 Consensus Envelope-Induced Broadly Binding Antibodies.

Journal Article AIDS Res Hum Retroviruses · August 2017 Antibodies that cross-react with multiple HIV-1 envelopes (Envs) are useful reagents for characterizing Env proteins and for soluble Env capture and purification assays. We previously reported 10 murine monoclonal antibodies induced by group M consensus En ... Full text Link to item Cite

Reducing V3 Antigenicity and Immunogenicity on Soluble, Native-Like HIV-1 Env SOSIP Trimers.

Journal Article J Virol · August 1, 2017 Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs) but can also expo ... Full text Link to item Cite

DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant.

Journal Article J Gen Virol · August 2017 The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses w ... Full text Link to item Cite

Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches.

Journal Article Immunity · June 20, 2017 The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens ... Full text Link to item Cite

Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge.

Journal Article Nat Commun · June 8, 2017 The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 mo ... Full text Link to item Cite

Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine.

Journal Article Viruses · June 2, 2017 The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity e ... Full text Link to item Cite

An HIV Envelope gp120-Fc Fusion Protein Elicits Effector Antibody Responses in Rhesus Macaques.

Journal Article Clin Vaccine Immunol · June 2017 A goal for HIV prevention programs is to develop safe, effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env ... Full text Link to item Cite

HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.

Journal Article J Virol · May 1, 2017 The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral ... Full text Link to item Cite

Superiority in Rhesus Macaques of Targeting HIV-1 Env gp140 to CD40 versus LOX-1 in Combination with Replication-Competent NYVAC-KC for Induction of Env-Specific Antibody and T Cell Responses.

Journal Article J Virol · May 1, 2017 We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env ... Full text Link to item Cite

Maternal Binding and Neutralizing IgG Responses Targeting the C-Terminal Region of the V3 Loop Are Predictive of Reduced Peripartum HIV-1 Transmission Risk.

Journal Article J Virol · May 1, 2017 The development of an effective maternal HIV-1 vaccine that could synergize with antiretroviral therapy (ART) to eliminate pediatric HIV-1 infection will require the characterization of maternal immune responses capable of blocking transmission of autologo ... Full text Link to item Cite

Randomized, Double-Blind Evaluation of Late Boost Strategies for HIV-Uninfected Vaccine Recipients in the RV144 HIV Vaccine Efficacy Trial.

Journal Article J Infect Dis · April 15, 2017 BACKGROUND: The RV144 ALVAC-HIV prime, AIDSVAX B/E boost afforded 60% efficacy against human immunodeficiency virus (HIV) acquisition at 1 year, waning to 31.2% after 3.5 years. We hypothesized that additional vaccinations might augment immune correlates o ... Full text Link to item Cite

Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users naïve to antiretroviral therapy.

Journal Article Sci Rep · April 7, 2017 Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and poten ... Full text Link to item Cite

Short Communication: Potential Risk of Replication-Competent Virus in HIV-1 Env-Pseudotyped Virus Preparations.

Journal Article AIDS Res Hum Retroviruses · April 2017 Env-pseudotyped viruses are valuable reagents for studies of HIV-1 neutralizing antibodies. It is often assumed that all pseudovirus particles are capable of only a single round of infection, making them a safe alternative to work with live HIV-1. In this ... Full text Link to item Cite

Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.

Journal Article Sci Transl Med · March 15, 2017 A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in indu ... Full text Link to item Cite

Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.

Journal Article Sci Transl Med · March 15, 2017 A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized ... Full text Link to item Cite

Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.

Journal Article Cell Rep · February 28, 2017 Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3 ... Full text Link to item Cite

Predictors of durable immune responses six months after the last vaccination in preventive HIV vaccine trials.

Journal Article Vaccine · February 22, 2017 BACKGROUND: The evaluation of durable immune responses is important in HIV vaccine research and development. The efficiency of such evaluation could be increased by incorporating predictors of the responses in the statistical analysis. In this paper, we in ... Full text Link to item Cite

DNA-MVA-protein vaccination of rhesus macaques induces HIV-specific immunity in mucosal-associated lymph nodes and functional antibodies.

Journal Article Vaccine · February 7, 2017 Successful future HIV vaccines are expected to generate an effective cellular and humoral response against the virus in both the peripheral blood and mucosal compartments. We previously reported the development of DNA-C and MVA-C vaccines based on HIV-1 su ... Full text Link to item Cite

Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial.

Journal Article PLoS Pathog · February 2017 UNLABELLED: The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V ... Full text Link to item Cite

Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.

Journal Article Sci Immunol · January 27, 2017 Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of di ... Full text Link to item Cite

Structure-based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies.

Journal Article J Biol Chem · January 6, 2017 A major goal for HIV-1 vaccine development is an ability to elicit strong and durable broadly neutralizing antibody (bNAb) responses. The trimeric envelope glycoprotein (Env) spikes on HIV-1 are known to contain multiple epitopes that are susceptible to bN ... Full text Link to item Cite

Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting.

Journal Article PLoS Pathog · January 2017 Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve p ... Full text Link to item Cite

Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development.

Journal Article Immunol Rev · January 2017 Induction of HIV-1 broadly neutralizing antibodies (bnAbs) to date has only been observed in the setting of HIV-1 infection, and then only years after HIV transmission. Thus, the concept has emerged that one path to induction of bnAbs is to define the vira ... Full text Link to item Cite

A Comparative Phase I Study of Combination, Homologous Subtype-C DNA, MVA, and Env gp140 Protein/Adjuvant HIV Vaccines in Two Immunization Regimes.

Journal Article Front Immunol · 2017 There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% indivi ... Full text Link to item Cite

Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women.

Journal Article PLoS One · 2017 BACKGROUND: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype ... Full text Link to item Cite

V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144.

Journal Article PLoS One · 2017 Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in RV144 Thai trial vaccine recipients, who were primed with a ... Full text Link to item Cite

Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults.

Journal Article PLoS One · 2017 BACKGROUND: A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines ... Full text Link to item Cite

HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers.

Journal Article PLoS One · 2017 Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neut ... Full text Link to item Cite

HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.

Journal Article PLoS One · 2017 Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation o ... Full text Link to item Cite

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

Journal Article Stat Commun Infect Dis · January 2017 BACKGROUND: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention ( ... Full text Link to item Cite

Broadly Neutralizing Antibody Responses in a Subset of HIV-1-Infected Individuals in Chennai, India.

Journal Article J Int Assoc Provid AIDS Care · 2017 Identification of broadly neutralizing antibodies (NAbs) generated during the course of HIV-1 infection is essential for effective HIV-1 vaccine design. The magnitude and breadth of neutralizing activity in the sera from 46 antiretroviral treatment-naive H ... Full text Link to item Cite

Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects.

Journal Article J Immunol · December 15, 2016 Diverse Ab effector functions mediated by the Fc domain have been commonly associated with reduced risk of infection in a growing number of nonhuman primate and human clinical studies. This study evaluated the anti-HIV Ab effector activities in polyclonal ... Full text Link to item Cite

Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques.

Journal Article JCI Insight · December 8, 2016 The ALVAC prime/ALVAC + AIDSVAX B/E boost RV144 vaccine trial induced an estimated 31% efficacy in a low-risk cohort where HIV‑1 exposures were likely at mucosal surfaces. An immune correlates study demonstrated that antibodies targeting the V2 region and ... Full text Link to item Cite

Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection.

Journal Article EBioMedicine · December 2016 HIV-1 infection occurs primarily through mucosal transmission. Application of biologically relevant mucosal models can advance understanding of the functional properties of antibodies that mediate HIV protection, thereby guiding antibody-based vaccine deve ... Full text Open Access Link to item Cite

Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques.

Journal Article Virol J · December 1, 2016 BACKGROUND: Increasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic s ... Full text Link to item Cite

Toll-like receptor 3 adjuvant in combination with virus-like particles elicit a humoral response against HIV.

Journal Article Vaccine · November 21, 2016 Human Immunodeficiency Virus (HIV) Virus-Like Particles (VLPs) composed of HIVIIIB Gag and HIVBaL gp120/gp41 envelope are a pseudovirion vaccine capable of presenting antigens in their native conformations. To enhance the immunogenicity of the HIV Env anti ... Full text Link to item Cite

Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001.

Journal Article J Virol · November 15, 2016 UNLABELLED: HIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years of infection, and therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 t ... Full text Link to item Cite

Increased Protein Degradation Improves Influenza Virus Nucleoprotein-Specific CD8+ T Cell Activation In Vitro but Not in C57BL/6 Mice.

Journal Article J Virol · November 15, 2016 UNLABELLED: Due to antigenic drift of influenza viruses, seasonal influenza vaccines need to be updated annually. These vaccines are based on predictions of strains likely to circulate in the next season. However, vaccine efficacy is greatly reduced in the ... Full text Link to item Cite

Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques.

Journal Article Mol Ther · November 2016 The design of an effective HIV-1 vaccine remains a major challenge. Several vaccine strategies based on viral vectors have been evaluated in preclinical and clinical trials, with largely disappointing results. Integrase defective lentiviral vectors (IDLV) ... Full text Open Access Link to item Cite

High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5α-Restrictive Macaques.

Journal Article J Immunol · November 1, 2016 We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/SIV macaque 239 vaccine. High doses of MVA ... Full text Link to item Cite

Effect of HIV-1 envelope cytoplasmic tail on adenovirus primed virus encoded virus-like particle immunizations.

Journal Article Vaccine · October 17, 2016 The low number of envelope (Env) spikes presented on native HIV-1 particles is a major impediment for HIV-1 prophylactic vaccine development. We designed virus-like particle encoding adenoviral vectors utilizing SIVmac239 Gag as an anchor for full length a ... Full text Link to item Cite

Induction of Heterologous Tier 2 HIV-1-Neutralizing and Cross-Reactive V1/V2-Specific Antibodies in Rabbits by Prime-Boost Immunization.

Journal Article J Virol · October 1, 2016 UNLABELLED: Poxvirus prime-protein boost used in the RV144 trial remains the only immunization strategy shown to elicit a modest level of protection against HIV-1 acquisition in humans. Although neutralizing antibodies (NAb) were generated, they were again ... Full text Link to item Cite

Virus-Like Particles Displaying Trimeric Simian Immunodeficiency Virus (SIV) Envelope gp160 Enhance the Breadth of DNA/Modified Vaccinia Virus Ankara SIV Vaccine-Induced Antibody Responses in Rhesus Macaques.

Journal Article J Virol · October 1, 2016 UNLABELLED: The encouraging results of the RV144 vaccine trial have spurred interest in poxvirus prime-protein boost human immunodeficiency virus (HIV) vaccine modalities as a strategy to induce protective immunity. Because vaccine-induced protective immun ... Full text Link to item Cite

Boosting of ALVAC-SIV Vaccine-Primed Macaques with the CD4-SIVgp120 Fusion Protein Elicits Antibodies to V2 Associated with a Decreased Risk of SIVmac251 Acquisition.

Journal Article J Immunol · October 1, 2016 The recombinant ALVAC vaccine coupled with the monomeric gp120/alum protein have decreased the risk of HIV and SIV acquisition. Ab responses to the V1/V2 regions have correlated with a decreased risk of virus acquisition in both humans and macaques. We hyp ... Full text Link to item Cite

Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity.

Journal Article EBioMedicine · October 2016 Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1) viruses or rare cases of vaccine-matched neutralization-resistant (tier-2) viruses, but no vaccine has induced antibodies that can broadly neutralize heter ... Full text Link to item Cite

Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C.

Journal Article PLoS Pathog · September 2016 We have investigated the immunogenicity in rabbits of native-like, soluble, recombinant SOSIP.664 trimers based on the env genes of four isolates of human immunodeficiency virus type 1 (HIV-1); specifically BG505 (clade A), B41 (clade B), CZA97 (clade C) a ... Full text Link to item Cite

Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies.

Journal Article Sci Immunol · July 29, 2016 Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. bnAbs occur in some HIV-1-infected individuals and frequently have characteristics of autoantibodies. We have studied cohorts of HIV-1-infected individuals who mad ... Full text Link to item Cite

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

Journal Article Nat Med · July 2016 A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the ... Full text Link to item Cite

Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization.

Journal Article PLoS Pathog · July 2016 The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority, however their potential effectiveness is challenged by very high HIV-1 envelope diversity. Two large prophylactic trials in high incidence, clad ... Full text Link to item Cite

Bispecific Antibodies Against HIV.

Journal Article Cell · June 16, 2016 Synergistic bispecific antibodies against HIV exhibit extraordinary potency and breadth of neutralization as promising candidates for treatment and prevention. ... Full text Link to item Cite

Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques.

Journal Article Proc Natl Acad Sci U S A · June 14, 2016 Most simian-human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding to rhesus CD4 (rhCD4) limits virus entry and replication a ... Full text Link to item Cite

Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap.

Journal Article Clin Vaccine Immunol · June 2016 A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following ... Full text Link to item Cite

Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk.

Journal Article J Virol · May 15, 2016 UNLABELLED: Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a mo ... Full text Open Access Link to item Cite

Derivation and Characterization of a CD4-Independent, Non-CD4-Tropic Simian Immunodeficiency Virus.

Journal Article J Virol · May 15, 2016 UNLABELLED: CD4 tropism is conserved among all primate lentiviruses and likely contributes to viral pathogenesis by targeting cells that are critical for adaptive antiviral immune responses. Although CD4-independent variants of human immunodeficiency virus ... Full text Link to item Cite

Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.

Journal Article Sci Transl Med · April 27, 2016 Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used ... Full text Link to item Cite

Long antibody HCDR3s from HIV-naïve donors presented on a PG9 neutralizing antibody background mediate HIV neutralization.

Journal Article Proc Natl Acad Sci U S A · April 19, 2016 Development of broadly neutralizing antibodies (bnAbs) against HIV-1 usually requires prolonged infection and induction of Abs with unusual features, such as long heavy-chain complementarity-determining region 3 (HCDR3) loops. Here we sought to determine w ... Full text Link to item Cite

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Journal Article Cell · April 7, 2016 Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived a ... Full text Link to item Cite

Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens.

Journal Article J Virol · April 2016 UNLABELLED: In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier cli ... Full text Open Access Link to item Cite

Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.

Journal Article J Immunol · April 1, 2016 Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutr ... Full text Link to item Cite

Elite neutralizers among HIV-1 Subtype-C infected individuals from southern India

Journal Article International Journal of Infectious Diseases · April 2016 Full text Cite

The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells.

Journal Article Mucosal Immunol · March 2016 Despite the risk of transmitting HIV-1, mothers in resource-poor areas are encouraged to breastfeed their infants because of beneficial immunologic and nutritional factors in milk. Interestingly, in the absence of antiretroviral prophylaxis, the overwhelmi ... Full text Link to item Cite

Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection.

Journal Article PLoS Pathog · March 2016 The identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct ... Full text Link to item Cite

Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083.

Journal Article J Infect Dis · February 15, 2016 BACKGROUND: Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune re ... Full text Link to item Cite

Enhanced Immune Responses to HIV-1 Envelope Elicited by a Vaccine Regimen Consisting of Priming with Newcastle Disease Virus Expressing HIV gp160 and Boosting with gp120 and SOSIP gp140 Proteins.

Journal Article J Virol · February 1, 2016 Newcastle disease virus (NDV) expressing HIV-1 BaL gp160 was evaluated either alone or with monomeric BaL gp120 and BaL SOSIP gp140 protein in a prime-boost combination in guinea pigs to enhance envelope (Env)-specific humoral and mucosal immune responses. ... Full text Link to item Cite

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

Journal Article Cell Rep · January 5, 2016 Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induc ... Full text Link to item Cite

Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.

Journal Article Open Forum Infect Dis · January 2016 Background.  In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency vi ... Full text Link to item Cite

Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques.

Journal Article PLoS One · 2016 Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitatio ... Full text Link to item Cite

Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques.

Journal Article PLoS One · 2016 Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein fused to a humanized anti-LOX-1 recombinant ant ... Full text Link to item Cite

Comparative Immunogenicity of HIV-1 gp140 Vaccine Delivered by Parenteral, and Mucosal Routes in Female Volunteers; MUCOVAC2, A Randomized Two Centre Study.

Journal Article PLoS One · 2016 BACKGROUND: Defining optimal routes for induction of mucosal immunity represents an important research priority for the HIV-1 vaccine field. In particular, it remains unclear whether mucosal routes of immunization can improve mucosal immune responses. METH ... Full text Link to item Cite

Engineering Recombinant Reoviruses To Display gp41 Membrane-Proximal External-Region Epitopes from HIV-1.

Journal Article mSphere · 2016 The gp41 membrane-proximal external region (MPER) is a target for broadly neutralizing antibody responses against human immunodeficiency virus type 1 (HIV-1). However, replication-defective virus vaccines currently under evaluation in clinical trials do no ... Full text Link to item Cite

Generation and Characterization of a Bivalent HIV-1 Subtype C gp120 Protein Boost for Proof-of-Concept HIV Vaccine Efficacy Trials in Southern Africa.

Journal Article PLoS One · 2016 The viral envelope glycoprotein (Env) is the major target for antibody (Ab)-mediated vaccine development against the Human Immunodeficiency Virus type 1 (HIV-1). Although several recombinant Env antigens have been evaluated in clinical trials, only the sur ... Full text Link to item Cite

Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.

Journal Article PLoS One · 2016 BACKGROUND: The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. ... Full text Link to item Cite

Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge.

Journal Article Mucosal Immunol · January 2016 There have been encouraging results for the development of an effective HIV vaccine. However, many questions remain regarding the quality of immune responses and the role of mucosal antibodies. We addressed some of these issues by using a simian immunodefi ... Full text Link to item Cite

Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.

Journal Article Cell · December 17, 2015 The envelope glycoprotein trimer mediates HIV-1 entry into cells. The trimer is flexible, fluctuating between closed and more open conformations and sometimes sampling the fully open, CD4-bound form. We hypothesized that conformational flexibility and tran ... Full text Link to item Cite

Dual-Affinity Re-Targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells.

Journal Article J Clin Invest · November 2, 2015 Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell-mediated clearance of HIV-1-infected cells. Specifically, we employed Dual-Affinity Re- ... Full text Link to item Cite

A Bivalent, Chimeric Rabies Virus Expressing Simian Immunodeficiency Virus Envelope Induces Multifunctional Antibody Responses.

Journal Article AIDS Res Hum Retroviruses · November 2015 We previously showed that a matrix (M) gene-deleted rabies virus (RABV)-based vaccine (RABV-ΔM) is highly immunogenic and induces potent B cell responses in the context of RABV infection. We speculated that RABV-ΔM expressing HIV proteins would also induce ... Full text Link to item Cite

Phenotypic Correlates of HIV-1 Macrophage Tropism.

Journal Article J Virol · November 2015 UNLABELLED: HIV-1 is typically CCR5 using (R5) and T cell tropic (T-tropic), targeting memory CD4(+) T cells throughout acute and chronic infections. However, viruses can expand into alternative cells types. Macrophage-tropic (M-tropic) HIV-1 variants have ... Full text Link to item Cite

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants.

Journal Article Viruses · October 21, 2015 Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that gener ... Full text Link to item Cite

Elite Control, Gut CD4 T Cell Sparing, and Enhanced Mucosal T Cell Responses in Macaca nemestrina Infected by a Simian Immunodeficiency Virus Lacking a gp41 Trafficking Motif.

Journal Article J Virol · October 2015 UNLABELLED: Deletion of Gly-720 and Tyr-721 from a highly conserved GYxxØ trafficking signal in the SIVmac239 envelope glycoprotein cytoplasmic domain, producing a virus termed ΔGY, leads to a striking perturbation in pathogenesis in rhesus macaques (Macac ... Full text Link to item Cite

Soluble Envelope Glycoprotein Trimers from a CD4-Independent HIV-1 Elicit Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies in Guinea Pigs.

Journal Article J Virol · October 2015 CD4-independent HIV-1 variants can infect coreceptor-expressing cells lacking CD4. The envelope (Env) glycoproteins on these HIV-1 variants expose a coreceptor binding site that overlaps some CD4-induced (CD4i) epitopes. Reports have demonstrated that CD4i ... Full text Link to item Cite

Characterization of protective immune response elicited by a trimeric envelope protein from an Indian clade C HIV-1 isolate in rhesus macaques.

Journal Article J Med Primatol · October 2015 BACKGROUND: Recent preclinical studies have demonstrated the use of properly folded trimeric HIV-1 envelope proteins as immunogen for eliciting protecting immune response in macaques. METHODS: Trimeric gp145 protein of Indian clade C HIV-1 (93IN101) was ch ... Full text Link to item Cite

Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.

Journal Article Nat Commun · September 29, 2015 A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory conce ... Full text Link to item Cite

Presenting native-like HIV-1 envelope trimers on ferritin nanoparticles improves their immunogenicity.

Journal Article Retrovirology · September 26, 2015 BACKGROUND: Presenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation. FINDINGS: We describe ferritin-based protein nanoparticles that display multiple copies of native-like HIV-1 envelope glycoprotein ... Full text Link to item Cite

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses.

Journal Article Cell Host Microbe · September 9, 2015 The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs e ... Full text Link to item Cite

An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates.

Journal Article J Virol · September 2015 UNLABELLED: The search for an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine remains a pressing need. The moderate success of the RV144 Thai clinical vaccine trial suggested that vaccine-induced HIV-1-specific antibodies can reduce the ris ... Full text Link to item Cite

HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies.

Journal Article Science · August 14, 2015 An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were highe ... Full text Link to item Cite

Comprehensive Characterization of the Transmitted/Founder env Genes From a Single MSM Cohort in China.

Journal Article J Acquir Immune Defic Syndr · August 1, 2015 BACKGROUND: The men having sex with men (MSM) population has become one of the major risk groups for HIV-1 infection in China. However, the epidemiological patterns, function of the env genes, and autologous and heterologous neutralization activity in the ... Full text Link to item Cite

Inhibitory Effect of Individual or Combinations of Broadly Neutralizing Antibodies and Antiviral Reagents against Cell-Free and Cell-to-Cell HIV-1 Transmission.

Journal Article J Virol · August 2015 UNLABELLED: To date, most therapeutic and vaccine candidates for human immunodeficiency virus type 1 (HIV-1) are evaluated preclinically for efficacy against cell-free viral challenges. However, cell-associated HIV-1 is suggested to be a major contributor ... Full text Link to item Cite

Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates.

Journal Article J Virol · August 2015 UNLABELLED: We compared the HIV-1-specific cellular and humoral immune responses elicited in rhesus macaques immunized with two poxvirus vectors (NYVAC and ALVAC) expressing the same HIV-1 antigens from clade C, Env gp140 as a trimeric cell-released protei ... Full text Link to item Cite

Vaccine-Induced Linear Epitope-Specific Antibodies to Simian Immunodeficiency Virus SIVmac239 Envelope Are Distinct from Those Induced to the Human Immunodeficiency Virus Type 1 Envelope in Nonhuman Primates.

Journal Article J Virol · August 2015 To evaluate antibody specificities induced by simian immunodeficiency virus (SIV) versus human immunodeficiency virus type 1 (HIV-1) envelope antigens in nonhuman primate (NHP), we profiled binding antibody responses to linear epitopes in NHP studies with ... Full text Link to item Cite

Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5- CD4 T Cell Responses in Rhesus Macaques.

Journal Article J Immunol · August 1, 2015 The goal of an HIV vaccine is to generate robust and durable protective Ab. Vital to this goal is the induction of CD4(+) T follicular helper (TFH) cells. However, very little is known about the TFH response to HIV vaccination and its relative contribution ... Full text Link to item Cite

Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.

Journal Article PLoS Pathog · August 2015 HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, t ... Full text Open Access Link to item Cite

Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

Journal Article PLoS Pathog · August 2015 Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre ... Full text Link to item Cite

Two-Year Follow-Up of Macaques Developing Intermittent Control of the Human Immunodeficiency Virus Homolog Simian Immunodeficiency Virus SIVmac251 in the Chronic Phase of Infection.

Journal Article J Virol · August 2015 UNLABELLED: Off-therapy control of viremia by HIV-infected individuals has been associated with two likely players: a restricted viral reservoir and an efficient cell-mediated immune response. We previously showed that a combination of highly suppressive a ... Full text Link to item Cite

Mucosal Immunization with Newcastle Disease Virus Vector Coexpressing HIV-1 Env and Gag Proteins Elicits Potent Serum, Mucosal, and Cellular Immune Responses That Protect against Vaccinia Virus Env and Gag Challenges.

Journal Article mBio · July 21, 2015 UNLABELLED: Newcastle disease virus (NDV) avirulent strain LaSota was used to coexpress gp160 Env and p55 Gag from a single vector to enhance both Env-specific and Gag-specific immune responses. The optimal transcription position for both Env and Gag genes ... Full text Link to item Cite

HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition.

Journal Article Sci Transl Med · July 15, 2015 In the RV144 vaccine trial, two antibody responses were found to correlate with HIV-1 acquisition. Because human leukocyte antigen (HLA) class II-restricted CD4(+) T cells are involved in antibody production, we tested whether HLA class II genotypes affect ... Full text Link to item Cite

HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers.

Journal Article Science · July 10, 2015 A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer t ... Full text Link to item Cite

Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission.

Journal Article J Clin Invest · July 1, 2015 Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune ... Full text Open Access Link to item Cite

Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost.

Journal Article J Virol · June 2015 UNLABELLED: An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4(+) and CD8(+) T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic ... Full text Link to item Cite

Redesigned HIV antibodies exhibit enhanced neutralizing potency and breadth.

Journal Article J Clin Invest · June 2015 Several HIV envelope-targeting (Env-targeting) antibodies with broad and potent neutralizing activity have been identified and shown to have unusual features. Of these, the PG9 antibody has a long heavy chain complementarity determining region 3 (HCDR3) an ... Full text Link to item Cite

Erratum: Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection (Proceedings of the National Academy of Sciences of the United States of America (2015) 112 (E992–E999) DOI: 10.1073/pnas.1423669112)

Other Proceedings of the National Academy of Sciences of the United States of America · May 5, 2015 The authors note that Fig. 3 appeared incorrectly. The corrected figure and its legend appear below. (Figure Presented). ... Full text Cite

Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site.

Journal Article PLoS Pathog · May 2015 Eliciting broad tier 2 neutralizing antibodies (nAbs) is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 2 of 8 rabbits immuni ... Full text Link to item Cite

Antigenicity and immunogenicity of a trimeric envelope protein from an Indian clade C HIV-1 isolate.

Journal Article J Biol Chem · April 3, 2015 Human immunodeficiency virus type 1 (HIV-1) isolates from India mainly belong to clade C and are quite distinct from clade C isolates from Africa in terms of their phylogenetic makeup, serotype, and sensitivity to known human broadly neutralizing monoclona ... Full text Link to item Cite

CD40L-adjuvanted DNA/modified vaccinia virus Ankara simian immunodeficiency virus (SIV) vaccine enhances protection against neutralization-resistant mucosal SIV infection.

Journal Article J Virol · April 2015 Here, we show that a CD40L-adjuvanted DNA/modified vaccinia virus Ankara (MVA) simian immunodeficiency virus (SIV) vaccine enhances protection against a pathogenic neutralization-resistant mucosal SIV infection, improves long-term viral control, and preven ... Full text Link to item Cite

DNA vaccine molecular adjuvants SP-D-BAFF and SP-D-APRIL enhance anti-gp120 immune response and increase HIV-1 neutralizing antibody titers.

Journal Article J Virol · April 2015 UNLABELLED: Broadly neutralizing antibodies (bNAbs) specific for conserved epitopes on the HIV-1 envelope (Env) are believed to be essential for protection against multiple HIV-1 clades. However, vaccines capable of stimulating the production of bNAbs rema ... Full text Link to item Cite

Potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying RNA vaccine expressing HIV type 1 envelope with a cationic nanoemulsion.

Journal Article J Infect Dis · March 15, 2015 Self-amplifying messenger RNA (mRNA) of positive-strand RNA viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well suited for global health applications. The SAM vaccine platfor ... Full text Link to item Cite

Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection.

Journal Article Proc Natl Acad Sci U S A · March 3, 2015 A guiding principle for HIV vaccine design has been that cellular and humoral immunity work together to provide the strongest degree of efficacy. However, three efficacy trials of Ad5-vectored HIV vaccines showed no protection. Transmission was increased i ... Full text Link to item Cite

Improving neutralization potency and breadth by combining broadly reactive HIV-1 antibodies targeting major neutralization epitopes.

Journal Article J Virol · March 2015 UNLABELLED: The isolation of broadly neutralizing HIV-1 monoclonal antibodies (MAbs) to distinct epitopes on the viral envelope glycoprotein (Env) provides the potential to use combinations of MAbs for prevention and treatment of HIV-1 infection. Since man ... Full text Link to item Cite

Infant HIV type 1 gp120 vaccination elicits robust and durable anti-V1V2 immunoglobulin G responses and only rare envelope-specific immunoglobulin A responses.

Journal Article J Infect Dis · February 15, 2015 BACKGROUND: Infant responses to vaccines can be impeded by maternal antibodies and immune system immaturity. It is therefore unclear whether human immunodeficiency virus type 1 (HIV-1) vaccination would elicit similar responses in adults and infants. METHO ... Full text Link to item Cite

Evaluation of humoral, mucosal, and cellular immune responses following co-immunization of HIV-1 Gag and Env proteins expressed by Newcastle disease virus.

Journal Article Hum Vaccin Immunother · 2015 The combination of multiple HIV antigens in a vaccine can broaden antiviral immune responses. In this study, we used NDV vaccine strain LaSota to generate rNDV (rLaSota/optGag) expressing human codon optimized p55 Gag protein of HIV-1. We examined the effe ... Full text Link to item Cite

Characterization of a Large Panel of Rabbit Monoclonal Antibodies against HIV-1 gp120 and Isolation of Novel Neutralizing Antibodies against the V3 Loop.

Journal Article PLoS One · 2015 We recently reported the induction of potent, cross-clade neutralizing antibodies (nAbs) against Human Immunodeficiency Virus type-1 (HIV-1) in rabbits using gp120 based on an M-group consensus sequence. To better characterize these antibodies, 93 hybridom ... Full text Link to item Cite

Immunogens Modeling a Fusion-Intermediate Conformation of gp41 Elicit Antibodies to the Membrane Proximal External Region of the HIV Envelope Glycoprotein.

Journal Article PLoS One · 2015 The membrane proximal external region (MPER) of the gp41 subunit of the HIV-1 envelope glycoprotein (Env) contains determinants for broadly neutralizing antibodies and has remained an important focus of vaccine design. However, creating an immunogen that e ... Full text Link to item Cite

Pharmacokinetics and immunogenicity of broadly neutralizing HIV monoclonal antibodies in macaques.

Journal Article PLoS One · 2015 The identification of highly potent broadly neutralizing antibodies (bnAbs) against HIV-1, and success in preventing SHIV infection following their passive administration, have increased the likelihood that immunotherapeutic strategies can be adopted to pr ... Full text Link to item Cite

Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved.

Journal Article Immunity · December 18, 2014 In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second v ... Full text Link to item Cite

Antibody to the gp120 V1/V2 loops and CD4+ and CD8+ T cell responses in protection from SIVmac251 vaginal acquisition and persistent viremia.

Journal Article J Immunol · December 15, 2014 The human papillomavirus pseudovirions (HPV-PsVs) approach is an effective gene-delivery system that can prime or boost an immune response in the vaginal tract of nonhuman primates and mice. Intravaginal vaccination with HPV-PsVs expressing SIV genes, comb ... Full text Link to item Cite

HIV-1 CD4-induced (CD4i) gp120 epitope vaccines promote B and T-cell responses that contribute to reduced viral loads in rhesus macaques.

Journal Article Virology · December 2014 To target the HIV CD4i envelope epitope, we primed rhesus macaques with replicating Ad-rhFLSC (HIV-1BaLgp120 linked to macaque CD4 D1 and D2), with or without Ad-SIVgag and Ad-SIVnef. Macaques were boosted with rhFLSC protein. Memory T-cells in PBMC, bronc ... Full text Link to item Cite

Impact of clade, geography, and age of the epidemic on HIV-1 neutralization by antibodies.

Journal Article J Virol · November 2014 UNLABELLED: Neutralizing antibodies (nAbs) are a high priority for vaccines that aim to prevent the acquisition of HIV-1 infection. Vaccine effectiveness will depend on the extent to which induced antibodies neutralize the global diversity of circulating H ... Full text Link to item Cite

HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial.

Journal Article J Clin Invest · November 2014 BACKGROUND. Vector prime-boost immunization strategies induce strong cellular and humoral immune responses. We examined the priming dose and administration order of heterologous vectors in HIV Vaccine Trials Network 078 (HVTN 078), a randomized, double-bli ... Full text Link to item Cite

A fusion intermediate gp41 immunogen elicits neutralizing antibodies to HIV-1.

Journal Article J Biol Chem · October 24, 2014 The membrane-proximal external region (MPER) of the human immunodeficiency virus, type 1 (HIV-1) envelope glycoprotein subunit gp41 is targeted by potent broadly neutralizing antibodies 2F5, 4E10, and 10E8. These antibodies recognize linear epitopes and ha ... Full text Link to item Cite

Aggregate complexes of HIV-1 induced by multimeric antibodies.

Journal Article Retrovirology · October 2, 2014 BACKGROUND: Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible muco ... Full text Open Access Link to item Cite

DNA vaccination by intradermal electroporation induces long-lasting immune responses in rhesus macaques.

Journal Article J Med Primatol · October 2014 BACKGROUND: A desirable HIV vaccine should induce protective long-lasting humoral and cellular immune responses. METHODS: Macaques were immunized by env DNA, selected from a panel of recently transmitted SIVmac251 Env using intradermal electroporation as v ... Full text Link to item Cite

Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques.

Journal Article J Exp Med · September 22, 2014 It is widely appreciated that effective human vaccines directed against viral pathogens elicit neutralizing antibodies (NAbs). The passive transfer of anti-HIV-1 NAbs conferring sterilizing immunity to macaques has been used to determine the plasma neutral ... Full text Link to item Cite

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.

Journal Article Cell Host Microbe · September 10, 2014 Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are ... Full text Link to item Cite

CD40L-adjuvanted DNA/modified vaccinia virus Ankara simian immunodeficiency virus SIV239 vaccine enhances SIV-specific humoral and cellular immunity and improves protection against a heterologous SIVE660 mucosal challenge.

Journal Article J Virol · September 1, 2014 UNLABELLED: It remains a challenge to develop a successful human immunodeficiency virus (HIV) vaccine that is capable of preventing infection. Here, we utilized the benefits of CD40L, a costimulatory molecule that can stimulate both dendritic cells (DCs) a ... Full text Link to item Cite

Envelope glycoprotein binding to the integrin α4β7 is not a general property of most HIV-1 strains.

Journal Article J Virol · September 2014 UNLABELLED: The HIV-1 surface glycoprotein gp120 has been reported to bind and signal through α4β7 by means of a tripeptide motif in the V2 loop that mimics structures present in the natural ligands for α4β7, suggesting that α4β7 may facilitate HIV-1 infec ... Full text Link to item Cite

FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial.

Journal Article J Clin Invest · September 2014 The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1-specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-spec ... Full text Link to item Cite

Analysis of HLA A*02 association with vaccine efficacy in the RV144 HIV-1 vaccine trial.

Journal Article J Virol · August 2014 UNLABELLED: The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31% against HIV-1 infection. Studies into possible correlates of protection found that antibodies specific to the V1 and V2 (V1/V2) region of envelope correlated inversely with infe ... Full text Link to item Cite

Humoral immunity induced by mucosal and/or systemic SIV-specific vaccine platforms suggests novel combinatorial approaches for enhancing responses.

Journal Article Clin Immunol · August 2014 Combinatorial HIV/SIV vaccine approaches targeting multiple arms of the immune system might improve protective efficacy. We compared SIV-specific humoral immunity induced in rhesus macaques by five vaccine regimens. Systemic regimens included ALVAC-SIVenv ... Full text Link to item Cite

Eliciting neutralizing antibodies with gp120 outer domain constructs based on M-group consensus sequence.

Journal Article Virology · August 2014 One strategy being evaluated for HIV-1 vaccine development is focusing immune responses towards neutralizing epitopes on the gp120 outer domain (OD) by removing the immunodominant, but non-neutralizing, inner domain. Previous OD constructs have not elicite ... Full text Link to item Cite

Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles.

Journal Article J Infect Dis · July 1, 2014 BACKGROUND: Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected a ... Full text Link to item Cite

Optimization and validation of a neutralizing antibody assay for HIV-1 in A3R5 cells.

Journal Article J Immunol Methods · July 2014 A3R5 is a human CD4(+) lymphoblastoid cell line that was engineered to express CCR5 and is useful for the detection of weak neutralizing antibody responses against tier 2 strains of HIV-1. Here we describe the optimization and validation of the HIV-1 neutr ... Full text Open Access Link to item Cite

HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities.

Journal Article J Virol · July 2014 The RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated vaccine efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site of immune pressure in the HIV-1 envelope (Env) variable region 2 (V2) focused on residue 169, which ... Full text Link to item Cite

Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein.

Journal Article J Immunol · June 15, 2014 Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserv ... Full text Link to item Cite

An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1.

Journal Article J Clin Invest · April 2014 Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnA ... Full text Link to item Cite

Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination.

Journal Article Sci Transl Med · March 19, 2014 HIV-1-specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass pro ... Full text Link to item Cite

Toll-like receptor 7/8 (TLR7/8) and TLR9 agonists cooperate to enhance HIV-1 envelope antibody responses in rhesus macaques.

Journal Article J Virol · March 2014 UNLABELLED: The development of a vaccine that can induce high titers of functional antibodies against HIV-1 remains a high priority. We have developed an adjuvant based on an oil-in-water emulsion that incorporates Toll-like receptor (TLR) ligands to test ... Full text Link to item Cite

A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus SIVmac251.

Journal Article J Virol · February 2014 As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of ... Full text Link to item Cite

Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.

Journal Article Nature · January 23, 2014 A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that ... Full text Open Access Link to item Cite

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.

Journal Article Retrovirology · January 20, 2014 BACKGROUND: A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circu ... Full text Link to item Cite

Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.

Journal Article PLoS One · 2014 UNLABELLED: In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cros ... Full text Link to item Cite

DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques.

Journal Article PLoS One · 2014 We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and m ... Full text Link to item Cite

Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization.

Journal Article PLoS One · 2014 Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env) in an adjuvant containing monophosphoryl lipid A (MPL) and QS21 (AS02A). Here, we compared differen ... Full text Link to item Cite

Transmitted/founder simian immunodeficiency virus envelope sequences in vesicular stomatitis and Semliki forest virus vector immunized rhesus macaques.

Journal Article PLoS One · 2014 Identification of transmitted/founder simian immunodeficiency virus (SIV) envelope sequences responsible for infection may prove critical for understanding HIV/SIV mucosal transmission. We used single genome amplification and phylogenetic analyses to chara ... Full text Link to item Cite

Importance of neutralization sieve analyses when seeking correlates of HIV-1 vaccine efficacy.

Other Hum Vaccin Immunother · 2014 This commentary describes a rationale for the use of breakthrough viruses from clinical trial participants to assess neutralizing antibodies as a correlate of HIV-1 vaccine efficacy. The rationale is based on principles of a genetic sieve analysis, where t ... Full text Link to item Cite

Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques.

Journal Article PLoS One · 2014 Eliciting neutralizing antibodies capable of inactivating a broad spectrum of HIV-1 strains is a major goal of HIV-1 vaccine design. The challenge is that envelopes (Envs) of circulating viruses are almost certainly different from any Env used in a vaccine ... Full text Link to item Cite

Resistance to infection, early and persistent suppression of simian immunodeficiency virus SIVmac251 viremia, and significant reduction of tissue viral burden after mucosal vaccination in female rhesus macaques.

Journal Article J Virol · January 2014 The efficacy of oral, intestinal, nasal, and vaginal vaccinations with DNA simian immunodeficiency virus (SIV)/interleukin-2 (IL-2)/IL-15, SIV Gag/Pol/Env recombinant modified vaccinia virus Ankara (rMVA), and AT-2 SIVmac239 inactivated particles was compa ... Full text Link to item Cite

Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.

Journal Article Antimicrob Agents Chemother · 2014 Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe ... Full text Link to item Cite

Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models.

Journal Article Virol J · December 2, 2013 BACKGROUND: Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine. METHODS: We have developed a computational approach that can identify key amin ... Full text Link to item Cite

Robust neutralizing antibodies elicited by HIV-1 JRFL envelope glycoprotein trimers in nonhuman primates.

Journal Article J Virol · December 2013 Host cell-mediated proteolytic cleavage of the human immunodeficiency virus type 1 (HIV-1) gp160 precursor glycoprotein into gp120 and gp41 subunits is required to generate fusion-competent envelope glycoprotein (Env) spikes. The gp120-directed broadly neu ... Full text Link to item Cite

Mitigation of variation observed in a peripheral blood mononuclear cell (PBMC) based HIV-1 neutralization assay by donor cell pooling.

Journal Article Virology · December 2013 Cultured primary peripheral blood mononuclear cells (PBMC) represent a potentially physiologic in vitro model of HIV-1 infection, but assessment of antibody-mediated HIV-1 neutralization using PBMC has been hindered by donor variability and lack of a susta ... Full text Link to item Cite

Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine.

Journal Article N Engl J Med · November 28, 2013 BACKGROUND: A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at in ... Full text Link to item Cite

Heterogeneity of Anti-V2 ADCC Ab Responses and Implications for Vaccine Development

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · November 1, 2013 Link to item Cite

Genetic and Immunological Evidence for a Role of Env-V3 Antibodies in the RV144 Trial

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · November 1, 2013 Link to item Cite

Effects of cellular activation on anti-HIV-1 restriction factor expression profile in primary cells.

Journal Article J Virol · November 2013 Expression of cell-intrinsic antiviral factors suppresses HIV-1 replication. We hypothesized that cellular activation modulates host restriction and susceptibility to HIV-1 infection. We measured the gene expression of 34 antiviral factors in healthy perip ... Full text Link to item Cite

Vaccination with Vaxfectin(®) adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia.

Journal Article Hum Vaccin Immunother · October 2013 We evaluated the immunogenicity and efficacy of Vaxfectin(®) adjuvanted SIV DNA vaccines in mice and macaques. Vaccination of mice with Vaxfectin(®) adjuvanted SIV gag DNA induced higher humoral immune responses than administration of unadjuvanted DNA, whe ... Full text Link to item Cite

Comparison of intradermal and intramuscular delivery followed by in vivo electroporation of SIV Env DNA in macaques.

Journal Article Hum Vaccin Immunother · October 2013 A panel of SIVmac251 transmitted Env sequences were tested for expression, function and immunogenicity in mice and macaques. The immunogenicity of a DNA vaccine cocktail expressing SIVmac239 and three transmitted SIVmac251 Env sequences was evaluated upon ... Full text Link to item Cite

Lack of B cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected African green monkeys.

Journal Article J Virol · October 2013 The design of an effective vaccine to reduce the incidence of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breastfeeding will require identification of protective immune responses that block postnatal virus acquisition. Nat ... Full text Open Access Link to item Cite

A novel rabbit monoclonal antibody platform to dissect the diverse repertoire of antibody epitopes for HIV-1 Env immunogen design.

Journal Article J Virol · September 2013 The majority of available monoclonal antibodies (MAbs) in the current HIV vaccine field are generated from HIV-1-infected people. In contrast, preclinical immunogenicity studies have mainly focused on polyclonal antibody responses in experimental animals. ... Full text Link to item Cite

Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice: selection against membrane proximal external region-associated autoreactivity limits T-dependent responses.

Journal Article J Immunol · September 1, 2013 A goal of HIV-1 vaccine development is to elicit broadly neutralizing Abs (BnAbs). Using a knock-in (KI) model of 2F5, a human HIV-1 gp41 membrane proximal external region (MPER)-specific BnAb, we previously demonstrated that a key obstacle to BnAb inducti ... Full text Link to item Cite

Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking.

Journal Article J Virol · September 2013 Experimental vaccine antigens based upon the HIV-1 envelope glycoproteins (Env) have failed to induce neutralizing antibodies (NAbs) against the majority of circulating viral strains as a result of antibody evasion mechanisms, including amino acid variabil ... Full text Link to item Cite

Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS.

Journal Article Retrovirology · July 16, 2013 BACKGROUND: HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus the ... Full text Link to item Cite

HIV-1 gp41 envelope IgA is frequently elicited after transmission but has an initial short response half-life.

Journal Article Mucosal Immunol · July 2013 Prevention of HIV-1 transmission at mucosal surfaces will likely require durable pre-existing mucosal anti-HIV-1 antibodies (Abs). Defining the ontogeny, specificities and potentially protective nature of the initial mucosal virus-specific B-cell response ... Full text Link to item Cite

Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees.

Journal Article J Virol · July 2013 The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent a ... Full text Open Access Link to item Cite

Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design.

Journal Article J Virol · July 2013 Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and ... Full text Link to item Cite

Mucosal immunization of lactating female rhesus monkeys with a transmitted/founder HIV-1 envelope induces strong Env-specific IgA antibody responses in breast milk.

Journal Article J Virol · June 2013 We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody respon ... Full text Link to item Cite

Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG.

Journal Article Proc Natl Acad Sci U S A · May 28, 2013 Analysis of correlates of risk of infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas HIV-1 Env-specific plasma IgA responses dire ... Full text Link to item Cite

Antibody-DEPENDENT, FcγRI-mediated neutralization of HIV-1 in TZM-bl cells occurs independently of phagocytosis.

Journal Article J Virol · May 2013 We previously showed that expression of human FcγRI on TZM-bl cells potentiates neutralization by gp41 membrane-proximal external region (MPER)-specific antibodies. Here we show that lysosomotropic reagents known to block phagocytosis do not diminish this ... Full text Link to item Cite

Identification of an HIV-1 clade A envelope that exhibits broad antigenicity and neutralization sensitivity and elicits antibodies targeting three distinct epitopes.

Journal Article J Virol · May 2013 Broadly neutralizing antibodies (bNAbs) PG9 and PG16 were isolated from an International AIDS Vaccine Initiative (IAVI) Protocol G subject infected with human immunodeficiency virus type 1 (HIV-1) clade A. Both antibodies are highly potent and neutralize g ... Full text Link to item Cite

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.

Journal Article Nature · April 25, 2013 Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide ... Full text Open Access Link to item Cite

Design of an Escherichia coli expressed HIV-1 gp120 fragment immunogen that binds to b12 and induces broad and potent neutralizing antibodies.

Journal Article J Biol Chem · April 5, 2013 b12, one of the few broadly neutralizing antibodies against HIV-1, binds to the CD4 binding site (CD4bs) on the gp120 subunit of HIV-1 Env. Two small fragments of HIV-1 gp120, b121a and b122a, which display about 70% of the b12 epitope and include solubili ... Full text Link to item Cite

Comparison of systemic and mucosal responses after DNA and protein co-immunization

Conference JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES · April 1, 2013 Link to item Cite

Magnitude, Breadth and Duration of HIV-1 Vaccine-Elicited Neutralizing Antibody Responses

Conference JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES · April 1, 2013 Link to item Cite

Antigenicity and immunogenicity of transmitted/founder, consensus, and chronic envelope glycoproteins of human immunodeficiency virus type 1.

Journal Article J Virol · April 2013 Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins were examined for their ability to bind human anti-HIV-1 monoclonal antibodies (MAbs) and then used ... Full text Link to item Cite

Immunogenicity of a vaccine regimen composed of simian immunodeficiency virus DNA, rMVA, and viral particles administered to female rhesus macaques via four different mucosal routes.

Journal Article J Virol · April 2013 A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles admin ... Full text Link to item Cite

Short communication: HIV type 1 subtype C variants transmitted through the bottleneck of breastfeeding are sensitive to new generation broadly neutralizing antibodies directed against quaternary and CD4-binding site epitopes.

Journal Article AIDS Res Hum Retroviruses · March 2013 Mother-to-child transmission of HIV-1 subtype C can occur in utero, intrapartum, or via breast milk exposure. While not well understood, there are putative differences in the mechanisms involved with the distinct routes of vertical HIV transmission. Here, ... Full text Link to item Cite

Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.

Journal Article J Virol · March 2013 We used the simian immunodeficiency virus mac251 (SIV(mac251)) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 ... Full text Link to item Cite

Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

Journal Article J Virol · February 2013 The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the l ... Full text Link to item Cite

Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.

Journal Article Immunity · January 24, 2013 The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial ... Full text Link to item Cite

Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants.

Journal Article Retrovirology · January 10, 2013 BACKGROUND: Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmit ... Full text Open Access Link to item Cite

Detection of HIV-1 neutralizing antibodies in a human CD4⁺/CXCR4⁺/CCR5⁺ T-lymphoblastoid cell assay system.

Journal Article PLoS One · 2013 Sensitive assays are needed to meaningfully assess low levels of neutralizing antibodies (NAbs) that may be important for protection against the acquisition of HIV-1 infection in vaccine recipients. The current assay of choice uses a non-lymphoid cell line ... Full text Link to item Cite

Pre-clinical development of a recombinant, replication-competent adenovirus serotype 4 vector vaccine expressing HIV-1 envelope 1086 clade C.

Journal Article PLoS One · 2013 BACKGROUND: There is a well-acknowledged need for an effective AIDS vaccine that protects against HIV-1 infection or limits in vivo viral replication. The objective of these studies is to develop a replication-competent, vaccine vector based on the adenovi ... Full text Link to item Cite

Impact of HIV-1 backbone on neutralization sensitivity: neutralization profiles of heterologous envelope glycoproteins expressed in native subtype C and CRF01_AE backbone.

Journal Article PLoS One · 2013 Standardized assays to assess vaccine and antiviral drug efficacy are critical for the development of protective HIV-1 vaccines and drugs. These immune assays will be advanced by the development of standardized viral stocks, such as HIV-1 infectious molecu ... Full text Link to item Cite

Stabilizing exposure of conserved epitopes by structure guided insertion of disulfide bond in HIV-1 envelope glycoprotein.

Journal Article PLoS One · 2013 Entry of HIV-1 into target cells requires binding of the viral envelope glycoprotein (Env) to cellular receptors and subsequent conformational changes that culminates in fusion of viral and target cell membranes. Recent structural information has revealed ... Full text Link to item Cite

Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial.

Journal Article PLoS One · 2013 The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B and E) was previously shown to have a 31.2% efficacy rate. Plasma specimens from vaccine and placebo recipients were use ... Full text Link to item Cite

Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems.

Journal Article PLoS One · 2013 Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs) has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT) of simian/human immunodeficiency virus (SHIV) in non-human primates and decreasing vi ... Full text Link to item Cite

Rational design of membrane proximal external region lipopeptides containing chemical modifications for HIV-1 vaccination.

Journal Article Clin Vaccine Immunol · January 2013 The inability to generate broadly neutralizing antibody (bnAb) responses to the membrane proximal external region (MPER) of HIV-1 gp41 using current vaccine strategies has hampered efforts to prevent the spread of HIV. To address this challenge, we investi ... Full text Link to item Cite

Administration of a Toll-like receptor 9 agonist decreases the proviral reservoir in virologically suppressed HIV-infected patients.

Journal Article PLoS One · 2013 Toll-like receptor (TLR) agonists can reactivate HIV from latently infected cells in vitro. We aimed to investigate the TLR-9 agonist, CPG 7909's in vivo effect on the proviral HIV reservoir and HIV-specific immunity. This was a post-hoc analysis of a doub ... Full text Link to item Cite

Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV.

Journal Article PLoS One · 2013 Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test th ... Full text Link to item Cite

Comparative Immunogenicity of Evolved V1V2-Deleted HIV-1 Envelope Glycoprotein Trimers.

Journal Article PLoS One · 2013 Despite almost 30 years of research, no effective vaccine has yet been developed against HIV-1. Probably such a vaccine would need to induce both an effective T cell and antibody response. Any vaccine component focused on inducing humoral immunity requires ... Full text Link to item Cite

Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial.

Journal Article PLoS One · 2013 Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced protection. Here, plasma IgG responses were assessed in three ... Full text Link to item Cite

Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector.

Journal Article PLoS One · 2013 The development of a vaccine against human immunodeficiency virus-1 (HIV-1) capable of inducing broad humoral and cellular responses at both the systemic and mucosal levels will be critical for combating the global AIDS epidemic. We previously demonstrated ... Full text Link to item Cite

Most rhesus macaques infected with the CCR5-tropic SHIV(AD8) generate cross-reactive antibodies that neutralize multiple HIV-1 strains.

Journal Article Proc Natl Acad Sci U S A · November 27, 2012 The induction of broadly reacting neutralizing antibodies has been a major goal of HIV vaccine research. Characterization of a pathogenic CCR5 (R5)-tropic SIV/HIV chimeric virus (SHIV) molecular clone (SHIV(AD8-EO)) revealed that eight of eight infected an ... Full text Link to item Cite

The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120.

Journal Article AIDS Res Hum Retroviruses · November 2012 The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antib ... Full text Link to item Cite

Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family.

Journal Article J Virol · November 2012 The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytoto ... Full text Link to item Cite

IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques.

Journal Article Hum Vaccin Immunother · November 1, 2012 Intramuscular injection of macaques with an IL-12 expression plasmid (0.1 or 0.4 mg DNA/animal) optimized for high level of expression and delivered using in vivo electroporation, resulted in the detection of systemic IL-12 cytokine in the plasma. Peak lev ... Full text Link to item Cite

Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines.

Journal Article Nat Med · November 2012 Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of ... Full text Link to item Cite

Profiles of neutralizing antibody response in chronically human immunodeficiency virus type 1 clade B'-infected former plasma donors from China naive to antiretroviral therapy.

Journal Article J Gen Virol · October 2012 Broadly neutralizing antibodies (NAbs) such as those generated in chronic human immunodeficiency virus type 1 (HIV-1) infection are considered a key component for an effective HIV-1 vaccine. Here, we measured NAb responses using a panel of 25 Env-pseudotyp ... Full text Link to item Cite

Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials.

Journal Article J Infect Dis · August 1, 2012 BACKGROUND: A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection ... Full text Link to item Cite

Pathogenicity and mucosal transmissibility of the R5-tropic simian/human immunodeficiency virus SHIV(AD8) in rhesus macaques: implications for use in vaccine studies.

Journal Article J Virol · August 2012 There is an urgent need to develop new pathogenic R5 simian/human immunodeficiency viruses (SHIVs) for the evaluation of candidate anti-HIV vaccines in nonhuman primates. Here, we characterize swarm SHIV(AD8) stocks, prepared from three infected rhesus mac ... Full text Link to item Cite

Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal.

Journal Article Retrovirology · July 17, 2012 BACKGROUND: We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV) resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R ... Full text Link to item Cite

The development of CD4 binding site antibodies during HIV-1 infection.

Journal Article J Virol · July 2012 Broadly neutralizing antibodies to the CD4 binding site (CD4bs) of gp120 are generated by some HIV-1-infected individuals, but little is known about the prevalence and evolution of this antibody response during the course of HIV-1 infection. We analyzed th ... Full text Link to item Cite

HIV-1 gp120 vaccine induces affinity maturation in both new and persistent antibody clonal lineages.

Journal Article J Virol · July 2012 Most antibodies that broadly neutralize HIV-1 are highly somatically mutated in antibody clonal lineages that persist over time. Here, we describe the analysis of human antibodies induced during an HIV-1 vaccine trial (GSK PRO HIV-002) that used the clade ... Full text Link to item Cite

Viral vectored granulocyte-macrophage colony stimulating factor inhibits vaccine protection in an SIV challenge model: protection correlates with neutralizing antibody.

Journal Article Vaccine · June 13, 2012 In a previous vaccine study, we reported significant and apparently sterilizing immunity to high-dose, mucosal, simian immunodeficiency virus (SIV) quasi-species challenge. The vaccine consisted of vectors based on vesicular stomatitis virus (VSV) expressi ... Full text Link to item Cite

Immune-correlates analysis of an HIV-1 vaccine efficacy trial.

Journal Article N Engl J Med · April 5, 2012 BACKGROUND: In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. METHODS: ... Full text Link to item Cite

Use of a polyanionic carbomer, Carbopol971P, in combination with MF59, improves antibody responses to HIV-1 envelope glycoprotein.

Journal Article Vaccine · April 5, 2012 Identification of optimal antigen(s) and adjuvant combination(s) to elicit potent, protective, and long-lasting immunity has been a major challenge for the development of effective vaccines against chronic viral pathogens, such as HIV-1, for which there ar ... Full text Link to item Cite

Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design.

Journal Article J Virol · April 2012 Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from ... Full text Open Access Link to item Cite

Replicating adenovirus-simian immunodeficiency virus (SIV) recombinant priming and envelope protein boosting elicits localized, mucosal IgA immunity in rhesus macaques correlated with delayed acquisition following a repeated low-dose rectal SIV(mac251) challenge.

Journal Article J Virol · April 2012 We have shown that sequential replicating adenovirus type 5 host range mutant human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) recombinant priming delivered first intranasally (i.n.) plus orally and then intratracheally (i.t.), followed ... Full text Link to item Cite

Targeting HIV-1 envelope glycoprotein trimers to B cells by using APRIL improves antibody responses.

Journal Article J Virol · March 2012 An HIV-1 vaccine remains elusive, in part because various factors limit the quantity and quality of the antibodies raised against the viral envelope glycoprotein complex (Env). We hypothesized that targeting Env vaccines directly to B cells, by fusing them ... Full text Link to item Cite

Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge.

Journal Article Vaccine · February 27, 2012 The current study assessed the immunogenicity and protective efficacy of various prime-boost vaccine regimens in rhesus macaques using combinations of recombinant DNA (rDNA), recombinant MVA (rMVA), and subunit gp140 protein. The rDNA and rMVA vectors were ... Full text Link to item Cite

SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses.

Journal Article Vaccine · February 21, 2012 BACKGROUND: Vaccine regimens using different agents for priming and boosting have become popular for enhancing T cell and Ab responses elicited by candidate HIV/AIDS vaccines. Here we use a simian model to evaluate immunogenicity and protective efficacy of ... Full text Link to item Cite

High-mannose glycan-dependent epitopes are frequently targeted in broad neutralizing antibody responses during human immunodeficiency virus type 1 infection.

Journal Article J Virol · February 2012 Broad and potent neutralizing antibody (BNAb) responses are rare in people infected by human immunodeficiency virus type 1 (HIV-1). Clearly defining the nature of BNAb epitopes on HIV-1 envelope glycoproteins (Envs) targeted in vivo is critical for future ... Full text Link to item Cite

Development and implementation of an international proficiency testing program for a neutralizing antibody assay for HIV-1 in TZM-bl cells.

Journal Article J Immunol Methods · January 31, 2012 Recent advances in assay technology have led to major improvements in how HIV-1 neutralizing antibodies are measured. A luciferase reporter gene assay performed in TZM-bl (JC53bl-13) cells has been optimized and validated. Because this assay has been adopt ... Full text Link to item Cite

Prime-boost regimens with adjuvanted synthetic long peptides elicit T cells and antibodies to conserved regions of HIV-1 in macaques.

Journal Article AIDS · January 28, 2012 OBJECTIVES: Administration of synthetic long peptides (SLPs) derived from human papillomavirus to cervical cancer patients resulted in clinical benefit correlated with expansions of tumour-specific T cells. Because vaginal mucosa is an important port of en ... Full text Link to item Cite

High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia.

Journal Article AIDS · January 14, 2012 OBJECTIVE: To characterize the correlates of protection from systemic infection in a vaccinated rhesus macaque, RAt-9, which had been challenged sequentially with two related clade C simian/human immunodeficiency viruses (SHIV-Cs) yet remained aviremic for ... Full text Link to item Cite

Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.

Journal Article PLoS Pathog · 2012 Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottle ... Full text Link to item Cite

Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape.

Journal Article PLoS Pathog · 2012 Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, ... Full text Link to item Cite

9G4 autoreactivity is increased in HIV-infected patients and correlates with HIV broadly neutralizing serum activity.

Journal Article PLoS One · 2012 The induction of a broadly neutralizing antibody (BNAb) response against HIV-1 would be a desirable feature of a protective vaccine. Vaccine strategies thus far have failed to elicit broadly neutralizing antibody responses; however a minority of HIV-infect ... Full text Link to item Cite

Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants.

Journal Article PLoS One · 2012 Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA), ... Full text Link to item Cite

An automated HIV-1 Env-pseudotyped virus production for global HIV vaccine trials.

Journal Article PLoS One · 2012 BACKGROUND: Infections with HIV still represent a major human health problem worldwide and a vaccine is the only long-term option to fight efficiently against this virus. Standardized assessments of HIV-specific immune responses in vaccine trials are essen ... Full text Link to item Cite

Isolation of monoclonal antibodies with predetermined conformational epitope specificity.

Journal Article PLoS One · 2012 Existing technologies allow isolating antigen-specific monoclonal antibodies (mAbs) from B cells. We devised a direct approach to isolate mAbs with predetermined conformational epitope specificity, using epitope mimetics (mimotopes) that reflect the three- ... Full text Link to item Cite

International network for comparison of HIV neutralization assays: the NeutNet report II.

Journal Article PLoS One · 2012 BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antib ... Full text Link to item Cite

Design and characterization of a peptide mimotope of the HIV-1 gp120 bridging sheet.

Journal Article Int J Mol Sci · 2012 The Bridging Sheet domain of HIV-1 gp120 is highly conserved among the HIV-1 strains and allows HIV-1 binding to host cells via the HIV-1 coreceptors. Further, the bridging sheet domain is a major target to neutralize HIV-1 infection. We rationally designe ... Full text Link to item Cite

The role of innate APOBEC3G and adaptive AID immune responses in HLA-HIV/SIV immunized SHIV infected macaques.

Journal Article PLoS One · 2012 The AID/APOBEC family (activation induced deaminase/apolipoprotein B mRNA editing cytokine deaminase) in B cells play important roles in adaptive and innate immunity. Whereas APOBEC3G has been studied in CD4+ T cells and myeloid cells its functional potent ... Full text Link to item Cite

Co-immunization with multimeric scaffolds and DNA rapidly induces potent autologous HIV-1 neutralizing antibodies and CD8+ T cells.

Journal Article PLoS One · 2012 To obtain proof of concept for HIV vaccines, we generated recombinant multimeric particles displaying the HIV-1 Envelope (Env) third hypervariable region (V3) as an N-terminal fusion protein on the E2 subunit of the pyruvate dehydrogenase complex of Geobac ... Full text Link to item Cite

International technology transfer of a GCLP-compliant HIV-1 neutralizing antibody assay for human clinical trials.

Journal Article PLoS One · 2012 The Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody-Vaccine Immune Monitoring Consortium (CAVD/CA-VIMC) assisted an international network of laboratories in transferring a validated assay used to judge HIV-1 vaccine immunogenicity in compli ... Full text Link to item Cite

Elicitation of neutralizing antibodies directed against CD4-induced epitope(s) using a CD4 mimetic cross-linked to a HIV-1 envelope glycoprotein.

Journal Article PLoS One · 2012 The identification of HIV-1 envelope glycoprotein (Env) structures that can generate broadly neutralizing antibodies (BNAbs) is pivotal to the development of a successful vaccine against HIV-1 aimed at eliciting effective humoral immune responses. To that ... Full text Link to item Cite

The role of natural killer (NK) cells and NK cell receptor polymorphisms in the assessment of HIV-1 neutralization.

Journal Article PLoS One · 2012 The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provid ... Full text Link to item Cite

Engineering, expression, purification, and characterization of stable clade A/B recombinant soluble heterotrimeric gp140 proteins.

Journal Article J Virol · January 2012 The envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is composed of two noncovalently associated subunits: an extracellular subunit (gp120) and a transmembrane subunit (gp41). The functional unit of Env on the surface of infectiou ... Full text Link to item Cite

Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques.

Journal Article Vaccine · December 9, 2011 The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region ... Full text Link to item Cite

Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals.

Journal Article J Virol · November 2011 A small proportion of HIV-infected individuals generate a neutralizing antibody (NAb) response of exceptional magnitude and breadth. A detailed analysis of the critical epitopes targeted by broadly neutralizing antibodies should help to define optimal targ ... Full text Link to item Cite

Dynamic antibody specificities and virion concentrations in circulating immune complexes in acute to chronic HIV-1 infection.

Journal Article J Virol · November 2011 Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent tr ... Full text Link to item Cite

Cross-reactive HIV-1-neutralizing human monoclonal antibodies identified from a patient with 2F5-like antibodies.

Journal Article J Virol · November 2011 The genes encoding broadly HIV-1-neutralizing human monoclonal antibodies (MAbs) are highly divergent from their germ line counterparts. We have hypothesized that such high levels of somatic hypermutation could pose a challenge for elicitation of the broad ... Full text Link to item Cite

Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.

Journal Article J Exp Med · October 24, 2011 The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we ... Full text Open Access Link to item Cite

Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors.

Journal Article J Virol · October 2011 V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificit ... Full text Link to item Cite

Detection of CD4-Binding Site Antibodies in Three HIV-1 Seroconverter Cohorts

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2011 Link to item Cite

Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins.

Journal Article J Virol · September 2011 Sexual transmission of human immunodeficiency virus type 1 (HIV-1) across mucosal barriers is responsible for the vast majority of new infections. This relatively inefficient process results in the transmission of a single transmitted/founder (T/F) virus, ... Full text Link to item Cite

epitopes immediately below the base of the V3 loop of gp120 as targets for the initial autologous neutralizing antibody response in two HIV-1 subtype B-infected individuals.

Journal Article J Virol · September 2011 Epitopes that drive the initial autologous neutralizing antibody response in HIV-1-infected individuals could provide insights for vaccine design. Although highly strain specific, these epitopes are immunogenic, vulnerable to antibody attack on infectious ... Full text Link to item Cite

HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies.

Journal Article J Virol · September 2011 Despite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies ... Full text Open Access Link to item Cite

The role of dynamin in HIV type 1 Env-mediated cell-cell fusion.

Journal Article AIDS Res Hum Retroviruses · September 2011 HIV-1 envelope glycoproteins are the key viral proteins that mediate HIV-1 entry and cell-cell fusion. In contrast to HIV-1 entry, the mechanism of HIV-1 Env-mediated cell-cell fusion is relatively unclear. This study demonstrated that dynasore, a dynamin ... Full text Link to item Cite

Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges.

Journal Article Vaccine · August 5, 2011 We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytog ... Full text Link to item Cite

High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses.

Journal Article Cytometry A · August 2011 We have developed a high-throughput platform to detect the presence of HIV-1 and SIV-specific ADCC-mediating antibody responses. The assay is based on the hydrolysis of a cell-permeable fluorogenic peptide substrate containing a sequence recognized by the ... Full text Link to item Cite

Construction and phenotypic characterization of HIV type 1 functional envelope clones of subtypes G and F.

Journal Article AIDS Res Hum Retroviruses · August 2011 Subtype G has been estimated to represent the fourth most prevalent clade in the HIV-1 pandemic and subtype F is widely circulating in parts of South America (frequently within BF recombinant forms) and in Romania. However, functional envelope clones of th ... Full text Link to item Cite

The genetic bottleneck in vertical transmission of subtype C HIV-1 is not driven by selection of especially neutralization-resistant virus from the maternal viral population.

Journal Article J Virol · August 2011 Subtype C human immunodeficiency virus type 1 (HIV-1C) continues to cause the majority of new cases of mother-to-child transmission (MTCT), and yet there are limited data on HIV-1C transmission. We amplified env from plasma RNA for 19 HIV-1C MTCT pairs, 10 ... Full text Link to item Cite

Functional cure of SIVagm infection in rhesus macaques results in complete recovery of CD4+ T cells and is reverted by CD8+ cell depletion.

Journal Article PLoS Pathog · August 2011 Understanding the mechanism of infection control in elite controllers (EC) may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled ... Full text Link to item Cite

Immunization with recombinant HLA classes I and II, HIV-1 gp140, and SIV p27 elicits protection against heterologous SHIV infection in rhesus macaques.

Journal Article J Virol · July 2011 Major histocompatibility complex (MHC) molecules expressed on the surface of human immunodeficiency virus (HIV) are potential targets for neutralizing antibodies. Since MHC molecules are polymorphic, nonself MHC can also be immunogenic. We have used combin ... Full text Link to item Cite

Prevention of infection by a granulocyte-macrophage colony-stimulating factor co-expressing DNA/modified vaccinia Ankara simian immunodeficiency virus vaccine.

Journal Article J Infect Dis · July 1, 2011 A simian immunodeficiency virus (SIV) vaccine coexpressing granulocyte-macrophage colony stimulating factor (GM-CSF) prevented infection in 71% of macaques that received 12 rectal challenges. The SIVsmE660 challenge had the tropism of incident human immuno ... Full text Link to item Cite

Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic.

Journal Article J Biol Chem · June 17, 2011 CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by the HIV co-receptor CCR5 and by CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown to elicit CD4i antibody responses in monkeys, which was correlated wi ... Full text Link to item Cite

Significant protection against high-dose simian immunodeficiency virus challenge conferred by a new prime-boost vaccine regimen.

Journal Article J Virol · June 2011 We constructed vaccine vectors based on live recombinant vesicular stomatitis virus (VSV) and a Semliki Forest virus (SFV) replicon (SFVG) that propagates through expression of the VSV glycoprotein (G). These vectors expressing simian immunodeficiency viru ... Full text Link to item Cite

LabKey Server NAb: a tool for analyzing, visualizing and sharing results from neutralizing antibody assays.

Journal Article BMC Immunol · May 27, 2011 BACKGROUND: Multiple types of assays allow sensitive detection of virus-specific neutralizing antibodies. For example, the extent of antibody neutralization of HIV-1, SIV and SHIV can be measured in the TZM-bl cell line through the degree of luciferase rep ... Full text Link to item Cite

Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys.

Journal Article Sci Transl Med · May 4, 2011 The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms ... Full text Link to item Cite

A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.

Journal Article J Infect Dis · April 15, 2011 BACKGROUND: A key missing element in the development of a successful human immunodeficiency virus (HIV) vaccine is an immunogen that can generate broadly cross-neutralizing antibodies against primary isolates of the virus. METHODS: This phase 1 clinical tr ... Full text Link to item Cite

Development of a tier 1 R5 clade C simian-human immunodeficiency virus as a tool to test neutralizing antibody-based immunoprophylaxis.

Journal Article J Med Primatol · April 2011 BACKGROUND: While some recently transmitted HIV clade C (HIV-C) strains exhibited tier 1 neutralization phenotypes, most were tier 2 strains (J Virol 2010; 84:1439). Because induction of neutralizing antibodies (nAbs) through vaccination against tier 2 vir ... Full text Link to item Cite

Mechanisms by which HIV envelope minimizes immunogenicity.

Journal Article Immunol Res · April 2011 With many viruses, vaccines containing the appropriate envelope antigens have provided strong and long lasting immunity. Not so with HIV-1 envelope, despite two decades of experience with various envelope and core constituent vaccines, protection provided ... Full text Link to item Cite

Long-term control of simian immunodeficiency virus mac251 viremia to undetectable levels in half of infected female rhesus macaques nasally vaccinated with simian immunodeficiency virus DNA/recombinant modified vaccinia virus Ankara.

Journal Article J Immunol · March 15, 2011 The efficacy of two SIV DNA plus recombinant modified vaccinia virus Ankara nasal vaccine regimens, one combined with plasmids expressing IL-2 and IL-15, the other with plasmids expressing GM-CSF, IL-12, and TNF-α, which may better stimulate humoral respon ... Full text Link to item Cite

Rapid SIV Env-specific mucosal and serum antibody induction augments cellular immunity in protecting immunized, elite-controller macaques against high dose heterologous SIV challenge.

Journal Article Virology · March 1, 2011 Three Indian rhesus macaques, Ad-SIV primed/protein boosted and exposed twice to high-dose mucosal SIV(mac251) challenges, exhibited elite control of viremia over 6.5 years. They were negative for host factors associated with control of SIV infection. Afte ... Full text Link to item Cite

Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles.

Journal Article J Infect Dis · March 1, 2011 BACKGROUND: Recombinant DNA and modified vaccinia virus Ankara (rMVA) vaccines represent a promising approach to an HIV/AIDS vaccine. This Phase 1 clinical trial compared the safety and immunogenicity of a rMVA vaccine administered with and without DNA vac ... Full text Link to item Cite

Origin and evolution of HIV-1 in breast milk determined by single-genome amplification and sequencing.

Journal Article J Virol · March 2011 HIV transmission via breastfeeding accounts for a considerable proportion of infant HIV acquisition. However, the origin and evolution of the virus population in breast milk, the likely reservoir of transmitted virus variants, are not well characterized. I ... Full text Open Access Link to item Cite

A phase I trial of preventive HIV vaccination with heterologous poxviral-vectors containing matching HIV-1 inserts in healthy HIV-uninfected subjects.

Journal Article Vaccine · February 24, 2011 We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara [MVA] and fowlpox [FPV]) in a homologous and heterologous vector prime-boost vaccination regimen containing matching HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 ... Full text Link to item Cite

Identification of amino acid substitutions associated with neutralization phenotype in the human immunodeficiency virus type-1 subtype C gp120.

Journal Article Virology · January 20, 2011 Neutralizing antibodies (Nabs) are thought to play an important role in prevention and control of HIV-1 infection and should be targeted by an AIDS vaccine. It is critical to understand how HIV-1 induces Nabs by analyzing viral sequences in both tested vir ... Full text Link to item Cite

Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection.

Journal Article PLoS One · 2011 A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We ... Full text Link to item Cite

A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204).

Journal Article PLoS One · 2011 BACKGROUND: The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegativ ... Full text Link to item Cite

Safety and immunogenicity of an HIV adenoviral vector boost after DNA plasmid vaccine prime by route of administration: a randomized clinical trial.

Journal Article PLoS One · 2011 BACKGROUND: In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor. METHODOLOGY/PRINCIPAL FINDINGS: This multicenter, open-label, randomized trial, HVTN 069, com ... Full text Link to item Cite

Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.

Journal Article PLoS One · 2011 Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP ... Full text Link to item Cite

B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4 T cell count, viral load and humoral immune responses.

Journal Article PLoS One · 2011 To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and ... Full text Link to item Cite

Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but does not diminish humoral immunity and efficacy of a DNA/MVA vaccine.

Journal Article J Immunol · December 15, 2010 The influence of preexisting immunity to viral vectors is a major issue for the development of viral-vectored vaccines. In this study, we investigate the effect of preexisting vaccinia virus immunity on the immunogenicity and efficacy of a DNA/modified vac ... Full text Link to item Cite

Profiles of human serum antibody responses elicited by three leading HIV vaccines focusing on the induction of Env-specific antibodies.

Journal Article PLoS One · November 9, 2010 In the current report, we compared the specificities of antibody responses in sera from volunteers enrolled in three US NIH-supported HIV vaccine trials using different immunization regimens. HIV-1 Env-specific binding antibody, neutralizing antibody, anti ... Full text Open Access Link to item Cite

Semi-solid gels function as physical barriers to human immunodeficiency virus transport in vitro.

Journal Article Antiviral Res · November 2010 Vaginal gels may act as physical barriers to HIV during sexual transmission. However, the extent and significance of this effect are not well understood. During male-to-female sexual transmission of HIV, semen containing infectious HIV is present within th ... Full text Link to item Cite

Neutralization activity in a geographically diverse East London cohort of human immunodeficiency virus type 1-infected patients: clade C infection results in a stronger and broader humoral immune response than clade B infection.

Journal Article J Gen Virol · November 2010 The array of human immunodeficiency virus (HIV) subtypes encountered in East London, an area long associated with migration, is unusually heterogeneous, reflecting the diverse geographical origins of the population. In this study it was shown that viral su ... Full text Open Access Link to item Cite

Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies.

Journal Article PLoS Comput Biol · October 7, 2010 A steady increase in knowledge of the molecular and antigenic structure of the gp120 and gp41 HIV-1 envelope glycoproteins (Env) is yielding important new insights for vaccine design, but it has been difficult to translate this information to an immunogen ... Full text Open Access Link to item Cite

GB virus type C envelope protein E2 elicits antibodies that react with a cellular antigen on HIV-1 particles and neutralize diverse HIV-1 isolates.

Journal Article J Immunol · October 1, 2010 Broadly neutralizing Abs to HIV-1 are well described; however, identification of Ags that elicit these Abs has proven difficult. Persistent infection with GB virus type C (GBV-C) is associated with prolonged survival in HIV-1-infected individuals, and amon ... Full text Link to item Cite

New broadly neutralizing human monoclonal antibodies targeting the 2F5 epitope

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2010 Link to item Cite

Magnitude and Breadth of the Neutralizing Antibody Response in RV144

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2010 Link to item Cite

Decrease in the Ratio of Infectious to Total Virions During Acute HIV-1 Infection

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2010 Link to item Cite

Improved DNA vaccination achieves long-lasting immune responses in macaques

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2010 Link to item Cite

Emergence of simian immunodeficiency virus-specific cytotoxic CD4+ T cells and increased humoral responses correlate with control of rebounding viremia in CD8-depleted macaques infected with Rev-independent live-attenuated simian immunodeficiency virus.

Journal Article J Immunol · September 15, 2010 Indian rhesus macaques infected with the Rev-independent live-attenuated SIVmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-SIV responses, and show no signs of immune deficiency. To analyze the immun ... Full text Link to item Cite

Recombinant varicella vaccines induce neutralizing antibodies and cellular immune responses to SIV and reduce viral loads in immunized rhesus macaques.

Journal Article Vaccine · September 7, 2010 The development of an effective AIDS vaccine remains one of the highest priorities in HIV research. The live, attenuated varicella-zoster virus (VZV) Oka vaccine, safe and effective for prevention of chickenpox and zoster, also has potential as a recombina ... Full text Link to item Cite

Magnitude and breadth of a nonprotective neutralizing antibody response in an efficacy trial of a candidate HIV-1 gp120 vaccine.

Journal Article J Infect Dis · August 15, 2010 BACKGROUND: A candidate vaccine consisting of human immunodeficiency virus type 1 (HIV-1) subunit gp120 protein was found previously to be nonprotective in an efficacy trial (Vax004) despite strong antibody responses against the vaccine antigens. Here we a ... Full text Open Access Link to item Cite

Comparative immunogenicity of HIV-1 clade C envelope proteins for prime/boost studies.

Journal Article PLoS One · August 11, 2010 BACKGROUND: Previous clinical efficacy trials failed to support the continued development of recombinant gp120 (rgp120) as a candidate HIV vaccine. However, the recent RV144 HIV vaccine trial in Thailand showed that a prime/boost immunization strategy invo ... Full text Open Access Link to item Cite

Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.

Journal Article PLoS One · August 10, 2010 BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). M ... Full text Open Access Link to item Cite

R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models.

Journal Article PLoS One · July 21, 2010 BACKGROUND: HIV-1 clade C (HIV-C) predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb) responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies th ... Full text Open Access Link to item Cite

HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity.

Journal Article PLoS One · June 15, 2010 The development of a topical microbicide blocking the sexual transmission of HIV-1 is urgently needed to control the global HIV/AIDS pandemic. The actinomycete-derived lectin actinohivin (AH) is highly specific to a cluster of high-mannose-type glycans uni ... Full text Open Access Link to item Cite

Vaccination with peptide mimetics of the gp41 prehairpin fusion intermediate yields neutralizing antisera against HIV-1 isolates.

Journal Article Proc Natl Acad Sci U S A · June 8, 2010 Eliciting a broadly neutralizing polyclonal antibody response against HIV-1 remains a major challenge. One approach to vaccine development is prevention of HIV-1 entry into cells by blocking the fusion of viral and cell membranes. More specifically, our go ... Full text Link to item Cite

Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease.

Journal Article Blood · April 15, 2010 One of the most puzzling observations in HIV research is the lack of pathogenicity in most nonhuman primate species that are natural hosts of simian immunodeficiency virus (SIV) infection. Despite this, natural hosts experience a level of viremia similar t ... Full text Link to item Cite

Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce beta-chemokines.

Journal Article J Exp Med · April 12, 2010 Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. ... Full text Open Access Link to item Cite

Quaternary epitope specificities of anti-HIV-1 neutralizing antibodies generated in rhesus macaques infected by the simian/human immunodeficiency virus SHIVSF162P4.

Journal Article J Virol · April 2010 Monoclonal antibodies (MAbs) that neutralize human immunodeficiency virus type 1 (HIV-1) have been isolated from HIV-1-infected individuals or animals immunized with recombinant HIV-1 envelope (Env) glycoprotein constructs. The epitopes of these neutralizi ... Full text Link to item Cite

Breadth of neutralizing antibodies elicited by stable, homogeneous clade A and clade C HIV-1 gp140 envelope trimers in guinea pigs.

Journal Article J Virol · April 2010 The native envelope (Env) spike on the surface of human immunodeficiency virus type 1 (HIV-1) is trimeric, and thus trimeric Env vaccine immunogens are currently being explored in preclinical immunogenicity studies. Key challenges have included the product ... Full text Link to item Cite

Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution.

Journal Article Proc Natl Acad Sci U S A · March 30, 2010 The conserved membrane-proximal external region (MPER) of HIV-1 envelope is a target for the rare broadly neutralizing 2F5, Z13, and 4E10 monoclonal antibodies (mAbs). One strategy to elicit such antibodies is to design an immunogen with increased exposure ... Full text Link to item Cite

Differential inhibition of human immunodeficiency virus type 1 in peripheral blood mononuclear cells and TZM-bl cells by endotoxin-mediated chemokine and gamma interferon production.

Journal Article AIDS Res Hum Retroviruses · March 2010 Bacterial lipopolysaccharide (endotoxin) is a frequent contaminant of biological specimens and is also known to be a potent inducer of beta-chemokines and other soluble factors that inhibit HIV-1 infection in vitro. Though lipopolysaccharide (LPS) has been ... Full text Open Access Link to item Cite

Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies.

Journal Article J Virol · February 2010 The restricted neutralization breadth of vaccine-elicited antibodies is a major limitation of current human immunodeficiency virus-1 (HIV-1) candidate vaccines. In order to permit the efficient identification of vaccines with enhanced capacity for elicitin ... Full text Link to item Cite

Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1.

Journal Article Virology · January 20, 2010 Neutralizing antibody (nAb) response is sporadic and has limited potency and breadth during infection with human immunodeficiency virus type 1 (HIV-1). In rare cases, broad and potent nAbs are actually induced in vivo. Identifying specific epitopes targete ... Full text Link to item Cite

Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

Journal Article PLoS One · January 20, 2010 BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central t ... Full text Open Access Link to item Cite

Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1.

Journal Article MAbs · 2010 Several human monoclonal antibodies (hmAbs) exhibit relatively potent and broad neutralizing activity against HIV-1, but there has not been much success in using them as potential therapeutics. We have previously hypothesized and demonstrated that small en ... Full text Open Access Link to item Cite

The role of antibodies in HIV vaccines.

Journal Article Annu Rev Immunol · 2010 Licensed vaccines against viral diseases generate antibodies that neutralize the infecting virus and protect against infection or disease. Similarly, an effective vaccine against HIV-1 will likely need to induce antibodies that prevent initial infection of ... Full text Link to item Cite

Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8+ T cell, and protect rhesus macaques from AIDS-like disease after SIV(mac251) challenge.

Journal Article Vaccine · December 11, 2009 Highly attenuated rabies virus (RV) vaccine vectors were evaluated for their ability to protect against highly pathogenic SIV(mac251) challenge. Mamu-A*01 negative rhesus macaques were immunized in groups of four with either: RV expressing SIV(mac239)-GagP ... Full text Link to item Cite

Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys.

Journal Article PLoS Pathog · December 2009 African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonna ... Full text Open Access Link to item Cite

Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines.

Journal Article Viruses · December 1, 2009 Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helper-dependent adeno ... Full text Link to item Cite

Nasal DNA-MVA SIV vaccination provides more significant protection from progression to AIDS than a similar intramuscular vaccination.

Journal Article Mucosal Immunol · November 2009 Preventive human immunodeficiency virus (HIV) vaccination may require induction of virus-specific immune responses at mucosal sites to contain viral infection locally after exposure, as most HIV infections occur through mucosal surfaces. We compared the ef ... Full text Link to item Cite

Derivation and characterization of a simian immunodeficiency virus SIVmac239 variant with tropism for CXCR4.

Journal Article J Virol · October 2009 Like human immunodeficiency virus type 1 (HIV-1), most simian immunodeficiency virus (SIV) strains use CCR5 to establish infection. However, while HIV-1 can acquire the ability to use CXCR4, SIVs that utilize CXCR4 have rarely been reported. To explore pos ... Full text Link to item Cite

Effect of B-cell depletion on viral replication and clinical outcome of simian immunodeficiency virus infection in a natural host.

Journal Article J Virol · October 2009 Simian immunodeficiency virus (SIV)-infected African nonhuman primates do not progress to AIDS in spite of high and persistent viral loads (VLs). Some authors consider the high viral replication observed in chronic natural SIV infections to be due to lower ... Full text Link to item Cite

Heterologous prime/boost immunizations of rhesus monkeys using chimpanzee adenovirus vectors.

Journal Article Vaccine · September 25, 2009 Pre-existing immunity to human adenovirus serotype 5 (AdHu5) has been shown to suppress the immunogenicity of recombinant Ad5 (rAdHu5) vector-based vaccines for human immunodeficiency virus type 1 (HIV-1) in both preclinical studies and clinical trials. As ... Full text Link to item Cite

DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge.

Journal Article Proc Natl Acad Sci U S A · September 15, 2009 Optimized plasmid DNAs encoding the majority of SIVmac239 proteins and delivered by electroporation (EP) elicited strong immune responses in rhesus macaques. Vaccination decreased viremia in both the acute and chronic phases of infection after challenge wi ... Full text Link to item Cite

Neutralizing antibodies against HIV-1: can we elicit them with vaccines and how much do we need?

Other Curr Opin HIV AIDS · September 2009 PURPOSE OF REVIEW: This review describes some of the major obstacles that have impeded progress in the development of an effective neutralizing antibody-based HIV-1 vaccine and explains why it may be possible to overcome these obstacles. A renewed interest ... Full text Link to item Cite

Protective efficacy of a single immunization of a chimeric adenovirus vector-based vaccine against simian immunodeficiency virus challenge in rhesus monkeys.

Journal Article J Virol · September 2009 Rare serotype and chimeric recombinant adenovirus (rAd) vectors that evade anti-Ad5 immunity are currently being evaluated as potential vaccine vectors for human immunodeficiency virus type 1 and other pathogens. We have recently reported that a heterologo ... Full text Link to item Cite

Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors.

Journal Article J Virol · September 2009 Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1- ... Full text Link to item Cite

Editorial introductions

Other Current Opinion in HIV and AIDS · September 1, 2009 Full text Cite

Enhanced HIV-1 neutralization by a CD4-VH3-IgG1 fusion protein.

Journal Article Biochem Biophys Res Commun · August 21, 2009 HIV-1 gp120 is an alleged B cell superantigen, binding certain VH3+ human antibodies. We reasoned that a CD4-VH3 fusion protein could possess higher affinity for gp120 and improved HIV-1 inhibitory capacity. To test this we produced several human IgG1 immu ... Full text Link to item Cite

Utilization of immunoglobulin G Fc receptors by human immunodeficiency virus type 1: a specific role for antibodies against the membrane-proximal external region of gp41.

Journal Article J Virol · August 2009 Receptors (FcgammaRs) for the constant region of immunoglobulin G (IgG) are an important link between humoral immunity and cellular immunity. To help define the role of FcgammaRs in determining the fate of human immunodeficiency virus type 1 (HIV-1) immune ... Full text Link to item Cite

Evidence that ecotropic murine leukemia virus contamination in TZM-bl cells does not affect the outcome of neutralizing antibody assays with human immunodeficiency virus type 1.

Journal Article J Virol · August 2009 The TZM-bl cell line that is commonly used to assess neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) was recently reported to be contaminated with an ecotropic murine leukemia virus (MLV) (Y. Takeuchi, M. O. McClure, and M. Pizz ... Full text Link to item Cite

Characterization of a trimeric MPER containing HIV-1 gp41 antigen.

Journal Article Virology · August 1, 2009 The membrane-proximal external region (MPER) of gp41 is considered as a prime target for the induction of neutralizing antibodies, since it contains the epitopes for three broadly neutralizing antibodies (2F5, 4E10 and Z13). Here we present a novel gp41 co ... Full text Link to item Cite

Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers.

Journal Article AIDS · May 15, 2009 OBJECTIVE: To determine the spectrum of antiviral antibodies in HIV-1-infected individuals in whom viral replication is spontaneously undetectable, termed HIV controllers (HICs). DESIGN: Multicenter French trial ANRS EP36 studying the viral control in HICs ... Full text Link to item Cite

Control of viremia and maintenance of intestinal CD4(+) memory T cells in SHIV(162P3) infected macaques after pathogenic SIV(MAC251) challenge.

Journal Article Virology · May 10, 2009 Recent HIV vaccine failures have prompted calls for more preclinical vaccine testing in non-human primates. However, similar to HIV infection of humans, developing a vaccine that protects macaques from infection following pathogenic SIV(MAC251) challenge h ... Full text Link to item Cite

High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination.

Journal Article Virology · May 10, 2009 Identifying the earliest neutralizing antibody specificities that are elicited following infection or vaccination by HIV-1 is an important objective of current HIV/AIDS vaccine research. We have shown previously that transplantation of HIV-1 V3 epitopes in ... Full text Link to item Cite

Preclinical studies of human immunodeficiency virus/AIDS vaccines: inverse correlation between avidity of anti-Env antibodies and peak postchallenge viremia.

Journal Article J Virol · May 2009 A major challenge for human immunodeficiency virus (HIV)/AIDS vaccines is the elicitation of anti-Env antibodies (Ab) capable of neutralizing the diversity of isolates in the pandemic. Here, we show that high-avidity, but nonneutralizing, Abs can have an i ... Full text Link to item Cite

Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain.

Journal Article Blood · April 30, 2009 We investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and ... Full text Link to item Cite

Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component.

Journal Article Proc Natl Acad Sci U S A · April 14, 2009 To prevent sexually transmitted HIV, the most desirable active ingredients of microbicides are antiretrovirals (ARVs) that directly target viral entry and avert infection at mucosal surfaces. However, most promising ARV entry inhibitors are biologicals, wh ... Full text Link to item Cite

In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth.

Journal Article J Virol · April 2009 The broadly neutralizing human monoclonal antibodies (MAbs) 2F5 and 4E10, both targeting the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope membrane proximal external region (MPER), are among the MAbs with the broadest heterologous n ... Full text Link to item Cite

High specific infectivity of plasma virus from the pre-ramp-up and ramp-up stages of acute simian immunodeficiency virus infection.

Journal Article J Virol · April 2009 To define the ratio of simian immunodeficiency virus (SIV) RNA molecules to infectious virions in plasma, a ramp-up-stage plasma pool was made from the earliest viral RNA (vRNA)-positive plasma samples (collected approximately 7 days after inoculation) fro ... Full text Link to item Cite

Highly complex neutralization determinants on a monophyletic lineage of newly transmitted subtype C HIV-1 Env clones from India.

Journal Article Virology · March 15, 2009 Little is known about the neutralization properties of HIV-1 in India to optimally design and test vaccines. For this reason, a functional Env clone was obtained from each of ten newly acquired, heterosexually transmitted HIV-1 infections in Pune, Maharash ... Full text Link to item Cite

Partial protection of Simian immunodeficiency virus (SIV)-infected rhesus monkeys against superinfection with a heterologous SIV isolate.

Journal Article J Virol · March 2009 Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infecti ... Full text Link to item Cite

International network for comparison of HIV neutralization assays: The NeutNet report

Journal Article PLoS ONE · February 20, 2009 Background: Neutralizing antibody assessments play a central role in human immunodeficiency virus type-1 (HIV-1) vaccine development but it is unclear which assay, or combination of assays, will provide reliable measures of correlates of protection. To add ... Full text Cite

Long-term vaccine protection from AIDS and clearance of viral DNA following SHIV89.6P challenge.

Journal Article Vaccine · February 11, 2009 In an earlier study, our group vaccinated rhesus macaques with vesicular stomatitis virus (VSV) vectors expressing Gag, Pol, and Env proteins from a hybrid simian/human immunodeficiency virus (SHIV). This was followed by a single boost with modified vaccin ... Full text Link to item Cite

Neutralization-sensitive R5-tropic simian-human immunodeficiency virus SHIV-2873Nip, which carries env isolated from an infant with a recent HIV clade C infection.

Journal Article J Virol · February 2009 Human immunodeficiency virus clade C (HIV-C) accounts for >56% of all HIV infections worldwide. To investigate vaccine safety and efficacy in nonhuman primates, a pathogenic, R5-tropic, neutralization-sensitive simian-human immunodeficiency virus (SHIV) ca ... Full text Link to item Cite

Simultaneous Evaluation of the Magnitude and Breadth of a Left and Right Censored Multivariate Response, with Application to HIV Vaccine Development.

Journal Article Stat Biopharm Res · February 1, 2009 Both the magnitude and breadth of neutralization against multiple strains of virus are main endpoints for comparing antibody-based HIV-1 vaccine candidates in Phase I and II trials, and are key markers to be evaluated in vaccine efficacy trials as immune c ... Full text Link to item Cite

Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys.

Journal Article Nature · January 1, 2009 A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency ... Full text Link to item Cite

Measuring HIV neutralization in a luciferase reporter gene assay.

Journal Article Methods Mol Biol · 2009 Neutralizing antibody (NAb) assays for human immunodeficiency virus (HIV) are used to study the immune response in infected individuals, to examine monoclonal antibodies and viral diversity, and to judge the potential value of candidate vaccine immunogens ... Full text Link to item Cite

Correlation of vaccine-elicited systemic and mucosal nonneutralizing antibody activities with reduced acute viremia following intrarectal simian immunodeficiency virus SIVmac251 challenge of rhesus macaques.

Journal Article J Virol · January 2009 Cell-mediated immunity and neutralizing antibodies contribute to control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection, but the role of nonneutralizing antibodies is not defined. Previously, we reported that sequential o ... Full text Link to item Cite

Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia.

Journal Article J Virol · December 2008 A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune resp ... Full text Link to item Cite

Profiling the specificity of neutralizing antibodies in a large panel of plasmas from patients chronically infected with human immunodeficiency virus type 1 subtypes B and C.

Journal Article J Virol · December 2008 Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigat ... Full text Link to item Cite

Immunogenicity and Neutralization Properties of a Trimeric MPER Containing gp41 Antigen

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2008 Link to item Cite

The use of nonhuman primate models in HIV vaccine development.

Journal Article PLoS Med · August 12, 2008 Cecilia Morgan and colleagues outline a two-stage nonhuman primate screening strategy for T cell-based HIV-1 vaccines. ... Full text Link to item Cite

Improved induction of antibodies against key neutralizing epitopes by human immunodeficiency virus type 1 gp120 DNA prime-protein boost vaccination compared to gp120 protein-only vaccination.

Journal Article J Virol · August 2008 A major challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development is to elicit potent and broadly neutralizing antibodies that are effective against primary viral isolates. Previously, we showed that DNA prime-protein boost vaccination u ... Full text Link to item Cite

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers.

Other Vaccine · July 23, 2008 An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of human immunodefici ... Full text Link to item Cite

Cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody that recognizes a novel conformational epitope on gp41 and lacks reactivity against self-antigens.

Journal Article J Virol · July 2008 Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear ep ... Full text Link to item Cite

An engineered Saccharomyces cerevisiae strain binds the broadly neutralizing human immunodeficiency virus type 1 antibody 2G12 and elicits mannose-specific gp120-binding antibodies.

Journal Article J Virol · July 2008 The glycan shield of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein serves as a barrier to antibody-mediated neutralization and plays a critical role in transmission and infection. One of the few broadly neutralizing HIV-1 antibodie ... Full text Link to item Cite

Recent advances in the characterization of HIV-1 neutralization assays for standardized evaluation of the antibody response to infection and vaccination.

Journal Article Virology · June 5, 2008 In AIDS vaccine development the pendulum has swung towards a renewed emphasis on the potential role for neutralizing antibodies in a successful global vaccine. It is recognized that vaccine-induced antibody performance, as assessed in the available neutral ... Full text Link to item Cite

Increased loss of CCR5+ CD45RA- CD4+ T cells in CD8+ lymphocyte-depleted Simian immunodeficiency virus-infected rhesus monkeys.

Journal Article J Virol · June 2008 Previously we have shown that CD8(+) T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4(+) T cells occurs in the intestinal tract of acutely infected macaques. To determine the i ... Full text Link to item Cite

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.

Journal Article Proc Natl Acad Sci U S A · May 27, 2008 The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathe ... Full text Link to item Cite

Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV89.6P challenge in Mamu-A*01 negative rhesus macaques.

Journal Article Virology · May 10, 2008 Previously, replicating adenovirus type 5 host range (Ad5hr)-HIV/SIV recombinant priming in combination with SIV envelope boosting, resulted in significant, durable protection in 39% of rhesus macaques after SIVmac251 challenge. Both Env-specific antibody ... Full text Link to item Cite

Transcytosis-blocking abs elicited by an oligomeric immunogen based on the membrane proximal region of HIV-1 gp41 target non-neutralizing epitopes.

Journal Article Curr HIV Res · May 2008 CTB-MPR(649-684), a translational fusion protein consisting of cholera toxin B subunit (CTB) and residues 649 684 of gp41 membrane proximal region (MPR), is a candidate vaccine aimed at blocking early steps of HIV-1 mucosal transmission. Bacterially produc ... Full text Link to item Cite

Analysis of the immune responses in chimpanzees infected with HIV type 1 isolates.

Journal Article AIDS Res Hum Retroviruses · April 2008 The mechanisms of resistance to AIDS development in HIV-1-infected chimpanzees have remained elusive. Unique among chimpanzees naturally or experimentally infected with HIV, several animals of the Yerkes cohort have progressed to clinical AIDS with selecti ... Full text Link to item Cite

Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope.

Journal Article Virology · March 15, 2008 Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we ge ... Full text Link to item Cite

DNA-MVA vaccine protection after X4 SHIV challenge in macaques correlates with day-of-challenge antiviral CD4+ cell-mediated immunity levels and postchallenge preservation of CD4+ T cell memory.

Journal Article AIDS Res Hum Retroviruses · March 2008 The ability of vaccines to induce immunity both in mucosal and systemic compartments may be required for prevention of HIV infection and AIDS. We compared DNA-MVA vaccination regimens adjuvanted by IL-12 DNA, administered intramuscularly and nasally or onl ... Full text Link to item Cite

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers.

Journal Article Vaccine · February 20, 2008 An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of Human Immunodefici ... Full text Link to item Cite

Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates.

Journal Article AIDS Res Hum Retroviruses · February 2008 Epidemiological and experimental data suggest that both robust neutralizing antibodies and potent cellular responses play important roles in controlling primary HIV-1 infection. In this study we have investigated the induction of systemic and mucosal immun ... Full text Link to item Cite

Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope.

Journal Article AIDS · January 30, 2008 BACKGROUND: Worldwide, the majority of human immunodeficiency virus (HIV) infections occur by heterosexual transmission. Thus, the development of a vaccine that can prevent intravaginal HIV infection is an important goal of AIDS vaccine research. OBJECTIVE ... Full text Link to item Cite

Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection.

Journal Article J Virol · January 2008 Two human monoclonal antibodies (MAbs) (2F5 and 4E10) against the human immunodeficiency virus type 1 (HIV-1) envelope g41 cluster II membrane proximal external region (MPER) broadly neutralize HIV-1 primary isolates. However, these antibody specificities ... Full text Link to item Cite

Betulinic acid derivatives that target gp120 and inhibit multiple genetic subtypes of human immunodeficiency virus type 1.

Journal Article Antimicrob Agents Chemother · January 2008 Betulinic acid (BA) derivatives can inhibit human immunodeficiency virus type 1 (HIV-1) entry or maturation depending on side chain modifications. While BA derivatives with antimaturation activity have attracted considerable interest, the anti-HIV-1 profil ... Full text Link to item Cite

Removal of a single N-linked glycan in human immunodeficiency virus type 1 gp120 results in an enhanced ability to induce neutralizing antibody responses.

Journal Article J Virol · January 2008 Glycans on human immunodeficiency virus (HIV) envelope protein play an important role in infection and evasion from host immune responses. To examine the role of specific glycans, we introduced single or multiple mutations into potential N-linked glycosyla ... Full text Link to item Cite

GM-CSF DNA: an adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccine.

Journal Article Virology · December 5, 2007 Single intradermal or intramuscular inoculations of GM-CSF DNA with the DNA prime for a simian-human immunodeficiency virus (SHIV)-89.6 vaccine, which consists of DNA priming followed by modified vaccinia Ankara (MVA) boosting, increased protection of both ... Full text Link to item Cite

Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine.

Journal Article J Virol · December 2007 A novel genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon launched from plasmid DNA is described. The plasmid encodes a VEE replicon under the transcriptional control of the cytomegalovirus immediate-early promoter (VEE ... Full text Link to item Cite

Immunogenicity in macaques of the clinical product for a clade B DNA/MVA HIV vaccine: elicitation of IFN-gamma, IL-2, and TNF-alpha coproducing CD4 and CD8 T cells.

Journal Article AIDS Res Hum Retroviruses · December 2007 The clinical product for a clade B HIV DNA/MVA vaccine expressing Gag, Pol, and Env has been tested for immunogenicity in macaques. Responding T cells were at the threshold for detection following DNA priming at weeks 0 and 8 but underwent sharp expansions ... Full text Link to item Cite

Standardized assessment of NAb responses elicited in rhesus monkeys immunized with single- or multi-clade HIV-1 envelope immunogens.

Journal Article Virology · October 10, 2007 The genetic diversity of HIV-1 envelope glycoproteins (Env) remains a major obstacle to the development of an antibody-based AIDS vaccine. The present studies examine the breadth and magnitude of neutralizing antibody (NAb) responses in rhesus monkeys afte ... Full text Link to item Cite

Lessons from a multisite international trial in the Caribbean and South America of an HIV-1 Canarypox vaccine (ALVAC-HIV vCP1452) with or without boosting with MN rgp120.

Journal Article J Acquir Immune Defic Syndr · October 1, 2007 BACKGROUND: The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial eva ... Full text Link to item Cite

A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120.

Journal Article Virology · September 30, 2007 To assess the potential of native Envelope glycoprotein (Env) trimers as neutralizing antibody vaccines, we immunized guinea pigs with three types of VLPs and soluble gp120. Particles included "SOS-VLPs" (bearing disulfide-shackled functional trimers), "UN ... Full text Link to item Cite

Recombinant modified vaccinia virus Ankara provides durable protection against disease caused by an immunodeficiency virus as well as long-term immunity to an orthopoxvirus in a non-human primate.

Journal Article Virology · September 15, 2007 Recombinant and non-recombinant modified vaccinia virus Ankara (MVA) strains are currently in clinical trials as human immunodeficiency virus-1 (HIV) and attenuated smallpox vaccines, respectively. Here we tested the ability of a recombinant MVA delivered ... Full text Link to item Cite

Heterologous prime/boost immunization of rhesus monkeys by using diverse poxvirus vectors.

Journal Article J Virol · August 2007 As the diversity of potential immunogens increases within certain classes of vectors, the possibility has arisen of employing heterologous prime/boost immunizations using diverse members of the same family of vectors. The present study was initiated to exp ... Full text Link to item Cite

GM-CSF as an adjuvant for protective immune responses

Conference JOURNAL OF MEDICAL PRIMATOLOGY · August 1, 2007 Link to item Cite

High throughput functional analysis of HIV-1 env genes without cloning.

Journal Article J Virol Methods · July 2007 Functional human immunodeficiency virus type 1 (HIV-1) env genes have been widely used for vaccine design, neutralization assays, and pathogenesis studies. However, obtaining bona fide functional env clones is a time consuming and labor intensive process. ... Full text Link to item Cite

Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state.

Journal Article Vaccine · June 28, 2007 The conserved membrane proximal external region (MPER) of the ectodomain of human immunodeficiency virus type 1 (HIV-1) gp41 is the target of two broadly neutralizing antibodies, 2F5 and 4E10. However, no neutralizing antibodies have been elicited against ... Full text Link to item Cite

Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV(89.6P) challenge in rhesus macaques.

Journal Article Vaccine · June 21, 2007 Plasmid-based IL-12 has been demonstrated to successfully enhance the immunogenicity of DNA vaccines, thus enabling a reduction of the amount of DNA required for immunization. IL-15 is thought to affect the maintenance and enhance effector function of CD8( ... Full text Link to item Cite

Cross-reactive HIV-1 neutralizing monoclonal antibodies selected by screening of an immune human phage library against an envelope glycoprotein (gp140) isolated from a patient (R2) with broadly HIV-1 neutralizing antibodies.

Journal Article Virology · June 20, 2007 Elicitation of broadly cross-reactive neutralizing antibodies (bcnAbs) in HIV infections is rare. To test the hypothesis that such antibodies could be elicited by HIV envelope glycoproteins (Envs) with unusual immunogenic properties and to identify novel b ... Full text Link to item Cite

Neutralizing and other antiviral antibodies in HIV-1 infection and vaccination.

Journal Article Curr Opin HIV AIDS · May 2007 PURPOSE OF REVIEW: New findings continue to support the notion that broadly crossreactive neutralizing antibody induction is a worthwhile and achievable goal for HIV-1 vaccines. Immunogens are needed that can overcome the genetic variability and complex im ... Full text Link to item Cite

Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques.

Journal Article J Virol · May 2007 Since human immunodeficiency virus (HIV)-specific cell-mediated immune (CMI) responses are critical in the early control and resolution of HIV infection and correlate with postchallenge outcomes in rhesus macaque challenge experiments, we sought to identif ... Full text Link to item Cite

Antiviral antibodies are necessary for control of simian immunodeficiency virus replication.

Journal Article J Virol · May 2007 To better define the role of B cells in the control of pathogenic simian immunodeficiency virus (SIV) replication, six rhesus monkeys were depleted of B cells by intravenous infusion of rituximab (anti-CD20) 28 days and 7 days before intravaginal SIVmac239 ... Full text Link to item Cite

A replication-competent adenovirus-human immunodeficiency virus (Ad-HIV) tat and Ad-HIV env priming/Tat and envelope protein boosting regimen elicits enhanced protective efficacy against simian/human immunodeficiency virus SHIV89.6P challenge in rhesus macaques.

Journal Article J Virol · April 2007 We previously demonstrated that replication-competent adenovirus (Ad)-simian immunodeficiency virus (SIV) recombinant prime/protein boost regimens elicit potent immunogenicity and strong, durable protection of rhesus macaques against SIV(mac251). Additiona ... Full text Link to item Cite

Highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6P Env and simian immunodeficiency virusmac239 Gag are safe in rhesus macaques and protect from an AIDS-like disease.

Journal Article J Infect Dis · April 1, 2007 We analyzed the safety and immunogenicity of attenuated rabies virus vectors expressing simian-human immunodeficiency virus (SHIV)-1(89.6P) Env or simian immunodeficiency virus (SIV)(mac239) Gag in rhesus macaques. Four test macaques were immunized with bo ... Full text Link to item Cite

Time dependence of protective post-exposure prophylaxis with human monoclonal antibodies against pathogenic SHIV challenge in newborn macaques.

Journal Article Virology · February 5, 2007 In a primate model of postnatal virus transmission, we have previously shown that 1 h post-exposure prophylaxis (PEP) with a triple combination of neutralizing monoclonal antibodies (nmAbs) conferred sterilizing protection to neonatal macaques against oral ... Full text Link to item Cite

Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial.

Journal Article J Acquir Immune Defic Syndr · February 1, 2007 BACKGROUND: A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp12 ... Full text Link to item Cite

Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers.

Journal Article Vaccine · January 5, 2007 BACKGROUND: Use of the recombinant proteins NefTat and gp120(W61D) formulated with the AS02A adjuvant system was previously shown to protect against AIDS in a rhesus macaque SHIV animal model system. METHODS: Eighty-four HIV uninfected human participants w ... Full text Link to item Cite

Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in Southern Africa.

Journal Article J Virol · December 2006 A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Z ... Full text Link to item Cite

Single epitope mucosal vaccine delivered via immuno-stimulating complexes induces low level of immunity against simian-HIV.

Journal Article Vaccine · November 17, 2006 The difficulty in developing an effective vaccine to contain the HIV/AIDS epidemic coupled with the fact that primary HIV-1 infection typically occurs via mucosal sites has increased emphasis on vaccine approaches that protect at mucosal surfaces. In this ... Full text Link to item Cite

An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains.

Journal Article J Acquir Immune Defic Syndr · November 1, 2006 Although HIV subtype B predominates in North America and Western Europe, most HIV infections worldwide are non-subtype B. Globally effective AIDS vaccines need to elicit broad immunity against multiple HIV strains. In this study, 10 chimpanzees were intran ... Full text Link to item Cite

A group M consensus envelope glycoprotein induces antibodies that neutralize subsets of subtype B and C HIV-1 primary viruses.

Journal Article Virology · September 30, 2006 HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a ce ... Full text Link to item Cite

Studies on GM-CSF DNA as an adjuvant for neutralizing Ab elicited by a DNA/MVA immunodeficiency virus vaccine.

Journal Article Virology · September 1, 2006 Here, we use a vaccine consisting of DNA priming followed by MVA boosting in rhesus macaques to investigate the ability of GM-CSF DNA to serve as an adjuvant for the elicitation of neutralizing Ab against an HIV-1 Env. The trial used Gag, Pol, and Env sequ ... Full text Link to item Cite

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates.

Journal Article Expert Rev Vaccines · August 2006 Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and com ... Full text Link to item Cite

Structured treatment interruptions with tenofovir monotherapy for simian immunodeficiency virus-infected newborn macaques.

Journal Article J Virol · July 2006 We demonstrated previously that prolonged tenofovir treatment of infant macaques, starting early during infection with virulent simian immunodeficiency virus (SIVmac251), can lead to persistently low or undetectable viremia even after the emergence of muta ... Full text Link to item Cite

Insensitivity of paediatric HIV-1 subtype C viruses to broadly neutralising monoclonal antibodies raised against subtype B.

Journal Article PLoS Med · July 2006 BACKGROUND: A Phase I clinical trial has been proposed that uses neutralising monoclonal antibodies (MAbs) as passive immunoprophylaxis to prevent mother-to-child transmission of HIV-1 in South Africa. To assess the suitability of such an approach, we dete ... Full text Link to item Cite

Excellent safety and tolerability of the human immunodeficiency virus type 1 pGA2/JS2 plasmid DNA priming vector vaccine in HIV type 1 uninfected adults.

Journal Article AIDS Res Hum Retroviruses · July 2006 A vaccine consisting of DNA priming followed by recombinant modified vaccinia Ankara (rMVA) boosting has achieved long-term control of a pathogenic challenge with a chimera of simian and human immunodeficiency viruses (SHIV-89.6P) in rhesus macaques. Based ... Full text Link to item Cite

Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge.

Journal Article J Exp Med · June 12, 2006 Acute simian immunodeficiency virus (SIV)/human immunodeficiency virus infection is accompanied by a massive destruction of CD4 memory T cells across all the tissue compartments. These early events set the course toward disease progression and immunodefici ... Full text Link to item Cite

Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys.

Journal Article Science · June 9, 2006 Vaccine-induced cellular immunity controls virus replication in simian immunodeficiency virus (SIV)-infected monkeys only transiently, leading to the question of whether such vaccines for AIDS will be effective. We immunized monkeys with plasmid DNA and re ... Full text Link to item Cite

Comparative evaluation of simian, simian-human, and human immunodeficiency virus infections in the pigtail macaque (Macaca nemestrina) model.

Journal Article AIDS Res Hum Retroviruses · June 2006 The global impact of HIV/AIDS intensifies the need for a preventive vaccine and nonhuman primate models can help provide critical insights into effective immunity. Pigtail macaques (Macaca nemestrina) are increasingly studied as a nonhuman primate model fo ... Full text Link to item Cite

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates.

Journal Article Expert Rev Vaccines · June 2006 Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and com ... Full text Link to item Cite

Immunization of rhesus macaques with a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 vaccine elicits protective antibody response against simian human immunodeficiency virus of R5 phenotype.

Journal Article Virology · May 10, 2006 The immunogenicity of a poylvalent HIV-1 vaccine comprised of Env antigens from primary R5 isolates was evaluated in rhesus macaques. DNA vaccines encoding four Env antigens from multiple HIV-1 subtypes and HIV-1 Gag antigen from a single subtype elicited ... Full text Link to item Cite

Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects rhesus macaques from CD4+ T-cell loss and reduces both systemic and mucosal simian-human immunodeficiency virus SHIVKU2 RNA levels.

Journal Article J Virol · April 2006 Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated the immunogenicity and relative efficacy of systemic immun ... Full text Link to item Cite

Analysis of HIV-1 subtype B third variable region peptide motifs for induction of neutralizing antibodies against HIV-1 primary isolates.

Journal Article Virology · February 5, 2006 The HIV-1 gp120 V3 loop is a potent inducer of neutralizing antibodies for T cell line adapted-HIV-1, but less so for primary isolates. We hypothesized that peptides representative of the diversity of natural HIV-1 V3 loop variants might capture elements o ... Full text Link to item Cite

Short communication: characteristics of effective immune control of simian/human immunodeficiency virus in pigtail macaques.

Journal Article AIDS Res Hum Retroviruses · January 2006 Considerable evidence suggests both HIV-specific T cells and neutralizing antibodies (nAb) can, separately, assist control of viremia. T cell and nAb responses were studied in detail in three pigtail macaques protected from chronic simian/human immunodefic ... Full text Link to item Cite

Studies using a viral challenge and CD8 T cell depletions on the roles of cellular and humoral immunity in the control of an SHIV-89.6P challenge in DNA/MVA-vaccinated macaques.

Journal Article Virology · December 20, 2005 Here, we study immune responses in four DNA/MVA-vaccinated macaques following an SHIV-89.6P challenge and a subsequent CD8 cell depletion. Both post-challenge and post-depletion peaks of viremia contracted with the expansion, or re-emergence, of CD8 T cell ... Full text Link to item Cite

Evaluation of CD8+ T-cell and antibody responses following transient increased viraemia in rhesus macaques infected with live, attenuated simian immunodeficiency virus.

Journal Article J Gen Virol · December 2005 In vivo depletion of CD8+ T cells results in an increase in viral load in macaques chronically infected with simian immunodeficiency virus (SIVmac239deltanef). Here, the cellular and humoral immune responses associated with this transient period of enhance ... Full text Link to item Cite

A combination DNA and attenuated simian immunodeficiency virus vaccine strategy provides enhanced protection from simian/human immunodeficiency virus-induced disease.

Journal Article J Virol · December 2005 Among the most effective vaccine candidates tested in the simian immunodeficiency virus (SIV)/macaque system, live attenuated viruses have been shown to provide the best protection from challenge. To investigate if preimmunization would increase the level ... Full text Link to item Cite

Induction of neutralizing antibodies against human immunodeficiency virus type 1 primary isolates by Gag-Env pseudovirion immunization.

Journal Article J Virol · December 2005 A major challenge for the development of an effective HIV vaccine is to elicit neutralizing antibodies against a broad array of primary isolates. Monomeric gp120-based vaccine approaches have not been successful in inducing this type of response, prompting ... Full text Link to item Cite

Evaluation of envelope vaccines derived from the South African subtype C human immunodeficiency virus type 1 TV1 strain.

Journal Article J Virol · November 2005 Human immunodeficiency virus type 1 (HIV-1) subtype C infections are on the rise in Sub-Saharan Africa and Asia. Therefore, there is a need to develop an HIV vaccine capable of eliciting broadly reactive immune responses against members of this subtype. We ... Full text Link to item Cite

Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660.

Journal Article Vaccine · October 10, 2005 VEE replicon particles (VRP), non-propagating vaccine vectors derived from Venezuelan equine encephalitis virus (VEE), were engineered to express immunogens from the cloned isolate SIVsmH-4, combined in a vaccine cocktail and inoculated subcutaneously to i ... Full text Link to item Cite

Mucosally-administered human-simian immunodeficiency virus DNA and fowlpoxvirus-based recombinant vaccines reduce acute phase viral replication in macaques following vaginal challenge with CCR5-tropic SHIVSF162P3.

Journal Article Vaccine · October 10, 2005 Further advances are required in understanding protection from AIDS by T cell immunity across mucosal sites of virus transmission. We analysed a set of multigenic HIV and SHIV DNA and Fowlpoxvirus (FPV) prime and boost vaccines for immunogenicity and prote ... Full text Link to item Cite

High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects.

Journal Article J Infect Dis · October 1, 2005 BACKGROUND: In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was cond ... Full text Link to item Cite

Polyvalent DNA prime and envelope protein boost HIV-1 vaccine elicits humoral and cellular responses and controls plasma viremia in rhesus macaques following rectal challenge with an R5 SHIV isolate.

Journal Article J Med Primatol · October 2005 Immunization of macaques with multivalent DNA encoding gp120 genes from HIV-1 subtypes A, B, C and E and a gag gene followed by boosting with homologous gp120 proteins elicited strong anti-gp120 antibodies capable of neutralizing homologous and to a lesser ... Full text Link to item Cite

Comparative immunogenicity in rhesus monkeys of multi-protein HIV-1 (CRF02_AG) DNA/MVA vaccines expressing mature and immature VLPs.

Journal Article Virology · September 15, 2005 We developed an AIDS vaccine for Western and West-Central Africa founded on HIV-1 subtype CRF02_AG. Rhesus macaques were primed with Gag-Pol-Env-expressing plasmid DNA and boosted with a recombinant modified vaccinia virus Ankara (rMVA), expressing matched ... Full text Link to item Cite

Human immunodeficiency virus type 1 subtype B ancestral envelope protein is functional and elicits neutralizing antibodies in rabbits similar to those elicited by a circulating subtype B envelope.

Journal Article J Virol · September 2005 Human immunodeficiency virus type 1 (HIV-1) is a difficult target for vaccine development, in part because of its ever-expanding genetic diversity and attendant capacity to escape immunologic recognition. Vaccine efficacy might be improved by maximizing im ... Full text Link to item Cite

Replicating rather than nonreplicating adenovirus-human immunodeficiency virus recombinant vaccines are better at eliciting potent cellular immunity and priming high-titer antibodies.

Journal Article J Virol · August 2005 A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report her ... Full text Link to item Cite

Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies.

Journal Article J Virol · August 2005 Induction of broadly cross-reactive neutralizing antibodies is a high priority for AIDS vaccine development but one that has proven difficult to be achieved. While most immunogens generate antibodies that neutralize a subset of T-cell-line-adapted strains ... Full text Link to item Cite

Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated rhesus macaques.

Journal Article J Virol · July 2005 Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. To test whet ... Full text Link to item Cite

Priming with plasmid DNAs expressing interleukin-12 and simian immunodeficiency virus gag enhances the immunogenicity and efficacy of an experimental AIDS vaccine based on recombinant vesicular stomatitis virus.

Journal Article AIDS Res Hum Retroviruses · July 2005 Of the various approaches being developed as prophylactic HIV vaccines, those based on a heterologous plasmid DNA prime, live vector boost vaccination regimen appear especially promising in the nonhuman primate/simian-human immunodeficiency virus (SHIV) ch ... Full text Link to item Cite

DNA vaccines expressing different forms of simian immunodeficiency virus antigens decrease viremia upon SIVmac251 challenge.

Journal Article J Virol · July 2005 We have tested the efficacy of DNA immunization as a single vaccination modality for rhesus macaques followed by highly pathogenic SIVmac251 challenge. To further improve immunogenicity of the native proteins, we generated expression vectors producing fusi ... Full text Link to item Cite

Pathogenicity of simian-human immunodeficiency virus SHIV-89.6P and SIVmac is attenuated in cynomolgus macaques and associated with early T-lymphocyte responses.

Journal Article J Virol · July 2005 Because most studies of AIDS pathogenesis in nonhuman primates have been performed in Indian-origin rhesus macaques (Macaca mulatta), little is known about lentiviral pathogenicity and control of virus replication following infection of alternative macaque ... Full text Link to item Cite

Enhanced potency of plasmid DNA microparticle human immunodeficiency virus vaccines in rhesus macaques by using a priming-boosting regimen with recombinant proteins.

Journal Article J Virol · July 2005 DNA vaccines have been used widely in experimental primate models of human immunodeficiency virus (HIV), but their effectiveness has been limited. In this study, we evaluated three technologies for increasing the potency of DNA vaccines in rhesus macaques. ... Full text Link to item Cite

Design, expression, and immunogenicity of a soluble HIV trimeric envelope fragment adopting a prefusion gp41 configuration.

Journal Article J Biol Chem · June 17, 2005 The human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env) is comprised of non-covalently associated gp120/gp41 subunits that form trimeric spikes on the virion surface. Upon binding to host cells, Env undergoes a series of structural transitio ... Full text Link to item Cite

Enhanced immunogenicity of gp120 protein when combined with recombinant DNA priming to generate antibodies that neutralize the JR-FL primary isolate of human immunodeficiency virus type 1.

Journal Article J Virol · June 2005 Strategies are needed for human immunodeficiency virus type 1 vaccine development that improves the neutralizing antibody response against primary isolates of the virus. Here we examined recombinant DNA priming followed by subunit protein boosting as a str ... Full text Link to item Cite

Expanded breadth of virus neutralization after immunization with a multiclade envelope HIV vaccine candidate.

Journal Article Vaccine · May 16, 2005 Although the V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) effectively elicits potent neutralizing antibody responses, the specificity of the antibody response is often restricted to T cell line adapted (TCLA) strains and a smal ... Full text Link to item Cite

HIV-1 neutralization by chimeric CD4-CG10 polypeptides fused to human IgG1.

Journal Article Mol Immunol · May 2005 The envelope glycoprotein of HIV-1 is the principal target for entry inhibitors. The use of soluble CD4 has been found to be impractical as most clinical isolates are resistant to neutralization at feasible concentrations. CG10 is one of a small group of m ... Full text Link to item Cite

Kinetics of expansion of SIV Gag-specific CD8+ T lymphocytes following challenge of vaccinated macaques.

Journal Article Virology · March 15, 2005 The ability of memory T cells to mount a recall response plays a key role in the ability of vaccinated animals to contain viral challenge. In this study, we intensively monitored the expansion of SIV Gag-specific CD8+ T cells in peripheral blood and tissue ... Full text Link to item Cite

Signature for long-term vaccine-mediated control of a Simian and human immunodeficiency virus 89.6P challenge: stable low-breadth and low-frequency T-cell response capable of coproducing gamma interferon and interleukin-2.

Journal Article J Virol · March 2005 In 2001, we reported 20 weeks of control of challenge with the virulent 89.6P chimera of simian and human immunodeficiency viruses (SHIV-89.6P) by a Gag-Pol-Env vaccine consisting of DNA priming and modified vaccinia virus Ankara boosting. Here we report t ... Full text Link to item Cite

Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants.

Journal Article Nat Immunol · March 2005 Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the ... Full text Link to item Cite

Protection of rhesus monkeys against infection with minimally pathogenic simian-human immunodeficiency virus: correlations with neutralizing antibodies and cytotoxic T cells.

Journal Article J Virol · March 2005 We studied the capacity of active immunization of rhesus monkeys with HIV-1 envelope protein (Env) to induce primary virus cross-reactive neutralizing antibodies to prevent infection following intravenous challenge with simian-human immunodeficiency virus ... Full text Link to item Cite

Simian immunodeficiency virus (SIV) envelope quasispecies transmission and evolution in infant rhesus macaques after oral challenge with uncloned SIVmac251: increased diversity is associated with neutralizing antibodies and improved survival in previously immunized animals.

Journal Article Virol J · February 14, 2005 BACKGROUND: Oral infection of infant macaques with simian immunodeficiency virus (SIV) is a useful animal model to test interventions to reduce postnatal HIV transmission via breast-feeding. We previously demonstrated that immunization of infant rhesus mac ... Full text Link to item Cite

Attenuated poxvirus-based simian immunodeficiency virus (SIV) vaccines given in infancy partially protect infant and juvenile macaques against repeated oral challenge with virulent SIV.

Journal Article J Acquir Immune Defic Syndr · February 1, 2005 An infant macaque model was developed to test pediatric vaccine candidates aimed at reducing HIV transmission through breast-feeding. Infant macaques were given multiple immunizations during the first 3 weeks of life with recombinant poxvirus vaccines expr ... Full text Link to item Cite

Neutralizing antibodies elicited by immunization of monkeys with DNA plasmids and recombinant adenoviral vectors expressing human immunodeficiency virus type 1 proteins.

Journal Article J Virol · January 2005 Immunization with recombinant serotype 5 adenoviral (rAd5) vectors or a combination of DNA plasmid priming and rAd5 boosting is known to elicit potent immune responses. However, little data exist regarding these immunization strategies and the development ... Full text Link to item Cite

Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type 1 group m consensus envelope glycoprotein.

Journal Article J Virol · January 2005 Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group ... Full text Link to item Cite

Timing of retroviral infection influences anamnestic immune response in vaccinated primates.

Journal Article Viral Immunol · 2005 Using simian immunodeficiency virus (SIV) infection of rhesus macaques to model human immunodeficiency virus (HIV) infection of humans, we assessed whether broadly reactive vaccine-induced humoral immunity would remain broadly reactive after viral challeng ... Full text Link to item Cite

Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies.

Journal Article AIDS Res Hum Retroviruses · January 2005 Designing an immunogen for effective neutralizing antibody induction against diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) is a high priority for HIV-1 vaccine development. Soluble gp120 envelope (Env) glycoprotein subunit vaccine ... Full text Link to item Cite

Novel adeno-associated virus vector vaccine restricts replication of simian immunodeficiency virus in macaques.

Journal Article J Virol · January 2005 Gene transfer vectors based on recombinant adeno-associated virus (rAAV) are simple, versatile, and safe. While the conventional applications for rAAV vectors have focused on delivery of therapeutic genes, we have developed the system for delivery of vacci ... Full text Link to item Cite

Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase reporter gene assays.

Journal Article Curr Protoc Immunol · January 2005 Neutralizing antibody assays are powerful tools for assessing humoral immunity in AIDS virus infection and vaccine development. Although many different assays have been described, all are based on the same principle, measuring reductions in virus infectivi ... Full text Link to item Cite

Editorial introductions

Other Current Opinion in Organ Transplantation · December 1, 2004 Cite

Efficacy of DNA and fowlpox virus priming/boosting vaccines for simian/human immunodeficiency virus.

Journal Article J Virol · December 2004 Further advances are required in understanding protection from AIDS by T-cell immunity. We analyzed a set of multigenic simian/human immunodeficiency virus (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficac ... Full text Link to item Cite

Immunogenicity study of glycoprotein-deficient rabies virus expressing simian/human immunodeficiency virus SHIV89.6P envelope in a rhesus macaque.

Journal Article J Virol · December 2004 Rabies virus (RV) has recently been developed as a novel vaccine candidate for human immunodeficiency virus type 1 (HIV-1). The RV glycoprotein (G) can be functionally replaced by HIV-1 envelope glycoprotein (Env) if the gp160 cytoplasmic domain (CD) of HI ... Full text Link to item Cite

Demographic factors that influence the neutralizing antibody response in recipients of recombinant HIV-1 gp120 vaccines.

Journal Article J Infect Dis · December 1, 2004 We compared neutralizing antibody responses in human immunodeficiency virus (HIV) type 1 gp120 vaccine recipients by age, sex, and race. Four phase 1 or 2 trials involving 505 vaccinated subjects were analyzed. Age and sex had no detectable effect on neutr ... Full text Link to item Cite

DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime.

Journal Article AIDS Res Hum Retroviruses · December 2004 Recently, a vaccine consisting of DNA priming followed by boosting with modified vaccinia Ankara (MVA) has provided long-term protection of rhesus macaques against a virulent challenge with a chimera of simian and human immunodeficiency viruses. Here, we r ... Full text Link to item Cite

Mucosal and systemic anti-HIV responses in rhesus macaques following combinations of intranasal and parenteral immunizations.

Journal Article AIDS Res Hum Retroviruses · November 2004 There is an urgent need to develop vaccines that can elicit immunological memory responses against HIV. Using the rhesus macaque model and a combination of intranasal (IN) and parenteral immunizations with DNA or protein adsorbed to microparticles or mixed ... Full text Link to item Cite

A comparative evaluation of nasal and parenteral vaccine adjuvants to elicit systemic and mucosal HIV-1 peptide-specific humoral immune responses in cynomolgus macaques.

Journal Article Vaccine · September 9, 2004 Cynomolgus macaques were immunized by either the intramuscular (i.m.) or intranasal (i.n.) route with a HIV-1 peptide-based immunogen (C4-V3 89.6P) alone, or formulated with novel adjuvants to evaluate the ability of the adjuvants to augment peptide-specif ... Full text Link to item Cite

Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody.

Journal Article J Virol · September 2004 The identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in our understanding of the mechanisms of virus entry and ne ... Full text Link to item Cite

Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein.

Journal Article Proc Natl Acad Sci U S A · August 31, 2004 Given the dual role of CD4 T cells as both immune effectors and targets for HIV infection, the balance of CD4 versus CD8 T cell-mediated responses induced by candidate AIDS vaccines may be critical in determining postvaccination infection outcomes. An atte ... Full text Link to item Cite

Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses.

Journal Article Proc Natl Acad Sci U S A · July 27, 2004 Although a consensus has emerged that an HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, the characteristics of an effective vaccine-induced T lymphocyte response remain unclear. We explored this issue in the simian human immunodeficienc ... Full text Link to item Cite

Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys.

Journal Article J Virol · July 2004 Because a strategy to elicit broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies has not yet been found, the role of an Env immunogen in HIV-1 vaccine candidates remains undefined. We sought to determine whether an HIV-1 Env im ... Full text Link to item Cite

Long-term memory B-cell responses in recipients of candidate human immunodeficiency virus type 1 vaccines.

Journal Article Vaccine · June 30, 2004 The efficacy and practical application of human immunodeficiency virus type 1 (HIV-1) vaccines may depend in part on the longevity of the immune responses generated, particularly those in the memory compartment. Candidate vaccines based on the HIV-1 envelo ... Full text Link to item Cite

Complete protection of neonatal rhesus macaques against oral exposure to pathogenic simian-human immunodeficiency virus by human anti-HIV monoclonal antibodies.

Journal Article J Infect Dis · June 15, 2004 Because milk-borne transmission of human immunodeficiency virus (HIV) diminishes the benefits of perinatal antiviral drug therapy in developing countries, we have developed a new strategy to prevent postnatal and, possibly, intrapartum virus transmission i ... Full text Link to item Cite

Passive immunotherapy in simian immunodeficiency virus-infected macaques accelerates the development of neutralizing antibodies.

Journal Article J Virol · June 2004 Passively transferred neutralizing antibodies can block lentivirus infection, but their role in postexposure prophylaxis is poorly understood. In this nonhuman-primate study, the effects of short-term antibody therapy on 5-year disease progression, virus l ... Full text Link to item Cite

Multiprotein HIV type 1 clade B DNA and MVA vaccines: construction, expression, and immunogenicity in rodents of the MVA component.

Journal Article AIDS Res Hum Retroviruses · June 2004 Recombinant modified vaccinia virus Ankara (MVA) expressing SIV or SHIV Gag-Pol and Env, alone or in conjunction with a related DNA vaccine, effectively controls immunodeficiency virus infections in nonhuman primates. Here we describe the construction, cha ... Full text Link to item Cite

Immunogenicity of constrained monoclonal antibody A32-human immunodeficiency virus (HIV) Env gp120 complexes compared to that of recombinant HIV type 1 gp120 envelope glycoproteins.

Journal Article J Virol · May 2004 One strategy for the generation of broadly reactive neutralizing antibodies (NA) against human immunodeficiency virus type 1 (HIV-1) primary isolates is to use immunogens that have constrained HIV-1 envelope gp120 conformations reflective of triggered enve ... Full text Link to item Cite

Immunogenicity of HIV-1 Env and Gag in baboons using a DNA prime/protein boost regimen.

Journal Article AIDS · April 30, 2004 OBJECTIVES: To evaluate the immunogenicity of sequence-modified HIV env and gag in baboons using DNA prime and protein boost strategy. METHODS: Synthetic sequence-modified HIV gene cassettes were constructed that expressed three different forms of Env prot ... Full text Link to item Cite

Highly effective control of an AIDS virus challenge in macaques by using vesicular stomatitis virus and modified vaccinia virus Ankara vaccine vectors in a single-boost protocol.

Journal Article J Virol · April 2004 Previous studies have shown that vaccination and boosting of rhesus macaques with attenuated vesicular stomatitis virus (VSV) vectors encoding Env and Gag proteins of simian immunodeficiency virus-human immunodeficiency virus (SHIV) hybrid viruses protect ... Full text Link to item Cite

Protective immunity to SIV challenge elicited by vaccination of macaques with multigenic DNA vaccines producing virus-like particles.

Journal Article AIDS Res Hum Retroviruses · April 2004 We utilized SIV(mne) infection of Macaca fascicularis to assess the efficacy of DNA vaccination alone, and as a priming agent in combination with subunit protein boosts. All SIV(mne) structural and regulatory genes were expressed using the human cytomegalo ... Full text Link to item Cite

Correlation between env V1/V2 region diversification and neutralizing antibodies during primary infection by simian immunodeficiency virus sm in rhesus macaques.

Journal Article J Virol · April 2004 Evolution of the domain encoding the V1/V2 variable region of the simian immunodeficiency virus sm (SIVsm) envelope (env) gene was analyzed in relation to route of virus challenge, virus load, and neutralizing antibody (NAb) titers during primary infection ... Full text Link to item Cite

Control of simian/human immunodeficiency virus viremia and disease progression after IL-2-augmented DNA-modified vaccinia virus Ankara nasal vaccination in nonhuman primates.

Journal Article J Immunol · March 15, 2004 A successful HIV vaccine may need to stimulate antiviral immunity in mucosal and systemic immune compartments, because HIV transmission occurs predominantly at mucosal sites. We report here the results of a combined DNA-modified vaccinia virus Ankara (MVA) ... Full text Link to item Cite

Immune failure in the absence of profound CD4+ T-lymphocyte depletion in simian immunodeficiency virus-infected rapid progressor macaques.

Journal Article J Virol · January 2004 A fraction of simian immunodeficiency virus (SIV)-infected macaques develop rapidly progressive disease in the apparent absence of detectable SIV-specific antibody responses. To characterize the immunopathogenesis of this syndrome, we studied viral load, C ... Full text Link to item Cite

Multispecific vaccine-induced mucosal cytotoxic T lymphocytes reduce acute-phase viral replication but fail in long-term control of simian immunodeficiency virus SIVmac239.

Journal Article J Virol · December 2003 Given the current difficulties generating vaccine-induced neutralizing antibodies to human immunodeficiency virus (HIV), the focus of the vaccine community has shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent reports of CTL-based ... Full text Link to item Cite

Gp120-alum boosting of a Gag-Pol-Env DNA/MVA AIDS vaccine: poorer control of a pathogenic viral challenge.

Journal Article AIDS Res Hum Retroviruses · October 2003 Envelope protein immunogens may improve DNA or live-vectored HIV vaccines by complementing antiviral cellular responses with Env antibodies. We tested this concept by administering two immunizations of alum-adjuvanted HIV-1 89.6 gp120 to macaques being pri ... Full text Link to item Cite

IL-12/GM-CSF coadministration in an SIV DNA prime/protein boost protocol enhances Gag-specific T cells but not virus-specific neutralizing antibodies in rhesus macaques.

Journal Article AIDS Res Hum Retroviruses · October 2003 Coadministration of pVecB7, a replication-defective SIV DNA vaccine, with interleukin-12 and GM-CSF expression plasmids, induced markedly enhanced control of viral replication and disease-free survival in macaques challenged intrarectally with pathogenic S ... Full text Link to item Cite

Cellular immunity elicited by human immunodeficiency virus type 1/ simian immunodeficiency virus DNA vaccination does not augment the sterile protection afforded by passive infusion of neutralizing antibodies.

Journal Article J Virol · October 2003 High levels of infused anti-human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibodies (MAbs) can completely protect macaque monkeys against mucosal chimeric simian-human immunodeficiency virus (SHIV) infection. Antibody levels below th ... Full text Link to item Cite

Purification, characterization, and immunogenicity of a soluble trimeric envelope protein containing a partial deletion of the V2 loop derived from SF162, an R5-tropic human immunodeficiency virus type 1 isolate.

Journal Article J Virol · October 2003 The envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the major target of neutralizing antibody responses and is likely to be a critical component of an effective vaccine against AIDS. Although monomeric HIV envelope subunit vac ... Full text Link to item Cite

Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses.

Journal Article J Virol · August 2003 Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, lit ... Full text Link to item Cite

Improved protection of rhesus macaques against intrarectal simian immunodeficiency virus SIV(mac251) challenge by a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen.

Journal Article J Virol · August 2003 In this study we investigated the ability of a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen to induce protective immunity in rhesus macaques against pathogenic simian immunodeficiency virus(mac251). Imm ... Full text Link to item Cite

Viremia control despite escape from a rapid and potent autologous neutralizing antibody response after therapy cessation in an HIV-1-infected individual.

Journal Article J Immunol · April 1, 2003 The neutralizing Ab response after primary HIV-1 infection is delayed relative to the virus-specific CD8(+) T cell response and the initial decline in plasma viremia. Because nearly all HIV-1 infections result in AIDS, it would be instructive to study case ... Full text Link to item Cite

Evidence for immune-mediated reduction of viral replication in Macaca nemestrina mucosally immunized with inactivated SHIV(89.6).

Journal Article Virology · March 30, 2003 Although most HIV-1 infections worldwide result from heterosexual transmission, most vaccine candidates have focused on induction of systemic immunity and protection. We hypothesized that combining systemic priming with mucosal boosting would induce mucosa ... Full text Link to item Cite

Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and alpha interferon responses.

Journal Article J Virol · March 2003 Attenuated primate lentivirus vaccines provide the most consistent protection against challenge with pathogenic simian immunodeficiency virus (SIV). Thus, they provide an excellent model to examine the influence of the route of immunization on challenge ou ... Full text Link to item Cite

Effect of humoral immune responses on controlling viremia during primary infection of rhesus monkeys with simian immunodeficiency virus.

Journal Article J Virol · February 2003 Cellular immune responses mediated by CD8+ lymphocytes exert efficient control of virus replication during primary simian immunodeficiency virus (SIV) infection. However, the role that antibodies may play in the early control of virus replication remains u ... Full text Link to item Cite

Enhancement of antibodies to the human immunodeficiency virus type 1 envelope by using the molecular adjuvant C3d.

Journal Article J Virol · February 2003 DNA vaccines expressing the envelope (Env) protein of the human immunodeficiency virus have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, the murine and human homol ... Full text Link to item Cite

A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIV(mac)251 challenge in rhesus Macaques.

Journal Article Vaccine · January 30, 2003 DNA vaccines are an important vaccine approach for many infectious diseases including human immunodeficiency virus (HIV). Recently, there have been exciting results reported for plasmid vaccination in pathogenic SHIV model systems. In these studies, plasmi ... Full text Link to item Cite

Prevention of disease induced by a partially heterologous AIDS virus in rhesus monkeys by using an adjuvanted multicomponent protein vaccine.

Journal Article J Virol · January 2003 Recombinant protein subunit AIDS vaccines have been based predominantly on the virus envelope protein. Such vaccines elicit neutralizing antibody responses that can provide type-specific sterilizing immunity, but in most cases do not confer protection agai ... Full text Link to item Cite

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.

Journal Article Nature · November 28, 2002 Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that ... Full text Link to item Cite

Live, attenuated simian immunodeficiency virus SIVmac-M4, with point mutations in the Env transmembrane protein intracytoplasmic domain, provides partial protection from mucosal challenge with pathogenic SIVmac251.

Journal Article J Virol · November 2002 Attenuated molecular clones of simian immunodeficiency virus (SIVmac) are important tools for studying the correlates of protective immunity to lentivirus infection in nonhuman primates. The most highly attenuated SIVmac mutants fail to induce disease but ... Full text Link to item Cite

Containment of simian immunodeficiency virus infection in vaccinated macaques: correlation with the magnitude of virus-specific pre- and postchallenge CD4+ and CD8+ T cell responses.

Journal Article J Immunol · November 1, 2002 Macaques infected with the SIV strain SIVmac251 develop a disease closely resembling human AIDS characterized by high viremia, progressive loss of CD4(+) T cells, occurrence of opportunistic infection, cachexia, and lymphomas. We report in this study that ... Full text Link to item Cite

Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapy.

Journal Article J Immunol · November 1, 2002 A cohort of rhesus macaques with long-standing SIVmac251 infection (> or =5 mo) was treated with continuous antiretroviral therapy (ART). A group of eight macaques was vaccinated with or without simultaneous administration of low dose IL-2 with the highly ... Full text Link to item Cite

Effects of cytotoxic T lymphocytes (CTL) directed against a single simian immunodeficiency virus (SIV) Gag CTL epitope on the course of SIVmac239 infection.

Journal Article J Virol · October 2002 Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency virus-challenged macaques. Therefore, we wanted to test the impact th ... Full text Link to item Cite

Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques.

Journal Article Proc Natl Acad Sci U S A · September 3, 2002 The identification of HIV envelope structures that generate broadly cross-reactive neutralizing antibodies is a major goal for HIV-vaccine development. In this study, we evaluated one such structure, expressed as either a gp120-CD4 or a gp140-CD4 complex, ... Full text Link to item Cite

Generation of neutralizing activity against human immunodeficiency virus type 1 in serum by antibody gene transfer.

Journal Article J Virol · September 2002 Although several human immunodeficiency virus (HIV) vaccine approaches have elicited meaningful antigen-specific T-cell responses in animal models, no single vaccine candidate has engendered antibodies that broadly neutralize primary isolates of HIV type 1 ... Full text Link to item Cite

Different patterns of immune responses but similar control of a simian-human immunodeficiency virus 89.6P mucosal challenge by modified vaccinia virus Ankara (MVA) and DNA/MVA vaccines.

Journal Article J Virol · August 2002 Recently we demonstrated the control of a mucosal challenge with a pathogenic chimera of simian and human immunodeficiency virus (SHIV-89.6P) by priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vacci ... Full text Link to item Cite

Protection by SIV VLP DNA prime/protein boost following mucosal SIV challenge is markedly enhanced by IL-12/GM-CSF co-administration.

Journal Article J Med Primatol · August 2002 The ever increasing number of people infected by human immunodeficiency virus (HIV) throughout the world renders the development of effective vaccines an urgent priority. Herein, we report on an attempt to induce and enhance antiviral responses using a deo ... Full text Link to item Cite

Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239.

Journal Article J Virol · July 2002 Producing a prophylactic vaccine for human immunodeficiency virus (HIV) has proven to be a challenge. Most biological isolates of HIV are difficult to neutralize, so that conventional subunit-based antibody-inducing vaccines are unlikely to be very effecti ... Full text Link to item Cite

Postnatal pre- and postexposure passive immunization strategies: protection of neonatal macaques against oral simian-human immunodeficiency virus challenge.

Journal Article J Med Primatol · June 2002 Simian-human immunodeficiency viruses (SHIV) allow the evaluation of antiviral strategies that target the envelope glycoproteins of the human immunodeficiency virus 1 (HIV-1) in macaques. We previously protected neonates from oral challenge with cell-free ... Full text Link to item Cite

Critical role for Env as well as Gag-Pol in control of a simian-human immunodeficiency virus 89.6P challenge by a DNA prime/recombinant modified vaccinia virus Ankara vaccine.

Journal Article J Virol · June 2002 Cellular immune responses against epitopes in conserved Gag and Pol sequences of human immunodeficiency virus type 1 have become popular targets for candidate AIDS vaccines. Recently, we used a simian-human immunodeficiency virus model (SHIV 89.6P) with ma ... Full text Link to item Cite

Modifications of the human immunodeficiency virus envelope glycoprotein enhance immunogenicity for genetic immunization.

Journal Article J Virol · June 2002 In this study, we have investigated the effect of specific mutations in human immunodeficiency virus type 1 (HIV-1) envelope (Env) on antibody production in an effort to improve humoral immune responses to this glycoprotein by DNA vaccination. Mice were in ... Full text Link to item Cite

Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF.

Journal Article Vaccine · May 22, 2002 Critical to the success of HIV-1 subunit vaccines is the development of strategies to augment vaccine immunogenicity. Successful adjuvants must not only improve immunogenicity above current adjuvant levels, but must also decrease the dose of immunogen requ ... Full text Link to item Cite

Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine.

Journal Article Vaccine · May 6, 2002 Heterologous prime/boost regimens have the potential for raising high levels of immune responses. Here, we report that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster has controlled a highly pathogenic immunodeficiency virus c ... Full text Link to item Cite

Molecular evolution of human immunodeficiency virus env in humans and monkeys: similar patterns occur during natural disease progression or rapid virus passage.

Journal Article J Virol · May 2002 Neonatal rhesus macaque 95-3 was inoculated with nonpassaged simian-human immunodeficiency virus strain SHIV-vpu(+), which encodes env of the laboratory-adapted human immunodeficiency virus (HIV) strain IIIB and is considered nonpathogenic. CD4(+) T-cell c ... Full text Link to item Cite

Neutralizing antibodies as a potential secondary protective mechanism during chronic SHIV infection in CD8+ T-cell-depleted macaques.

Journal Article AIDS · April 12, 2002 OBJECTIVE: To directly examine the role of CD8+ T cells in controlling viremia and disease during chronic, low-level primate immunodeficiency virus infection in DNA prime/protein boost-vaccinated macaques. BACKGROUND: A cohort of macaques, vaccinated with ... Full text Link to item Cite

Comparison of vaccine strategies using recombinant env-gag-pol MVA with or without an oligomeric Env protein boost in the SHIV rhesus macaque model.

Journal Article Virology · March 15, 2002 Rhesus macaques were immunized with a replication-deficient vaccinia virus (MVA) expressing human immunodeficiency virus type 1 89.6 envelope (env) and SIV gagpol (MVA/SHIV89.6) with or without a protein boost consisting of soluble 89.6 env (gp140). Immuni ... Full text Link to item Cite

Regional clustering of shared neutralization determinants on primary isolates of clade C human immunodeficiency virus type 1 from South Africa.

Journal Article J Virol · March 2002 Clade C is one of the most prevalent genetic subtypes of human immunodeficiency virus type 1 (HIV-1) in the world today and one of the least studied with respect to neutralizing antibodies. Most information on HIV-1 serology as it relates to neutralization ... Full text Link to item Cite

Safety and immunogenicity of a high-titered canarypox vaccine in combination with rgp120 in a diverse population of HIV-1-uninfected adults: AIDS Vaccine Evaluation Group Protocol 022A.

Journal Article J Acquir Immune Defic Syndr · March 1, 2002 To test the safety and immunogenicity of a high-titered preparation of ALVAC-HIV vCP205 in both high-risk and low-risk persons and to evaluate variations in dosing schedule, we conducted a multicenter, randomized, double-blind trial of this vector in combi ... Full text Link to item Cite

DNA prime/protein boost vaccine strategy in neonatal macaques against simian human immunodeficiency virus.

Journal Article J Med Primatol · February 2002 Newborn macaques were vaccinated against a chimeric simian human immunodeficiency (SHIV) virus, SHIV-vpu+, by DNA priming and boosting with homologous HIV-1 gp160. Following SHIV-vpu+ challenge, containment of infection was observed in 4 of 15 animals give ... Full text Link to item Cite

Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes.

Journal Article Nature · January 17, 2002 Potent virus-specific cytotoxic T lymphocyte (CTL) responses elicited by candidate AIDS vaccines have recently been shown to control viral replication and prevent clinical disease progression after pathogenic viral challenges in rhesus monkeys. Here we sho ... Full text Link to item Cite

Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity.

Journal Article Nature · January 17, 2002 Recent studies of human immunodeficiency virus type 1 (HIV-1) infection in humans and of simian immunodeficiency virus (SIV) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are me ... Full text Link to item Cite

Prospects for vaccine protection against HIV-1 infection and AIDS.

Journal Article Annu Rev Immunol · 2002 The rapid and devastating spread of the AIDS epidemic in the developing world as well as the difficulties associated with delivering antiretroviral drugs in affected countries underscore the urgent need for the development of a safe and effective AIDS vacc ... Full text Link to item Cite

ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency.

Journal Article J Virol · January 2002 T-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication after infection. Both vaccination- and infection-induced T-cell responses are dependent ... Full text Link to item Cite

Rev-independent simian immunodeficiency virus strains are nonpathogenic in neonatal macaques.

Journal Article J Virol · January 2002 The viral protein Rev is essential for the export of the subset of unspliced and partially spliced lentiviral mRNAs and the production of structural proteins. Rev and its RNA binding site RRE can be replaced in both human immunodeficiency virus (HIV) and s ... Full text Link to item Cite

Alphavirus replicon particles as candidate HIV vaccines.

Journal Article IUBMB Life · 2002 Replicon particles based on Venezuelan equine encephalitis virus (VEE) contain a self-replicating RNA encoding the VEE replicase proteins and expressing a gene of interest in place of the viral structural protein genes. Structural proteins for packaging of ... Full text Link to item Cite

Heterologous neutralizing antibody induction in a simian-human immunodeficiency virus primate model: lack of original antigenic sin.

Journal Article J Infect Dis · December 15, 2001 According to the principle of original antigenic sin, neutralizing antibodies (NAbs) initially directed against a single virus strain compromise the immune system's ability to subsequently mount adequate responses against antigenically divergent virus stra ... Full text Link to item Cite

Resistance to neutralizing antibody and expanded coreceptor usage are associated with human immunodeficiency virus type 1 isolates derived from chimpanzees with pathogenic infections.

Journal Article AIDS Res Hum Retroviruses · December 10, 2001 Immunologic and biologic factors associated with the progression to AIDS in HIV-1-infected chimpanzees were investigated. Chimpanzee C499 was euthanized in 1996 as a result of the development of AIDS approximately 11 years after infection with HIV-1. At th ... Full text Link to item Cite

The stoichiometry of trimeric SIV glycoprotein interaction with CD4 differs from that of anti-envelope antibody Fab fragments.

Journal Article J Biol Chem · November 16, 2001 Human and simian immunodeficiency viruses infect host lymphoid cells by binding CD4 molecules via their gp160 envelope glycoproteins. Biochemical studies on recombinant SIVmac32H (pJ5) envelope ectodomain gp140 precursor protein show that the envelope is a ... Full text Link to item Cite

Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects.

Journal Article Proc Natl Acad Sci U S A · November 6, 2001 The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subject ... Full text Link to item Cite

Neutralizing antibodies associated with viremia control in a subset of individuals after treatment of acute human immunodeficiency virus type 1 infection.

Journal Article J Virol · November 2001 Immediate treatment of acute human immunodeficiency virus type 1 (HIV-1) infection has been associated with subsequent control of viremia in a subset of patients after therapy cessation, but the immune responses contributing to control have not been fully ... Full text Link to item Cite

Vaccine-elicited immune responses prevent clinical AIDS in SHIV(89.6P)-infected rhesus monkeys.

Journal Article Immunol Lett · November 1, 2001 Accumulating evidence has demonstrated the importance of cytotoxic T lymphocytes (CTLs) and helper T lymphocytes in controlling HIV-1 replication. We have elicited immune responses in rhesus monkeys utilizing DNA vaccines augmented by the administration of ... Full text Link to item Cite

An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants.

Journal Article Cell · September 7, 2001 We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AI ... Full text Link to item Cite

Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge.

Journal Article J Virol · August 2001 To develop prophylaxis against mother-to-child human immunodeficiency virus (HIV) transmission, we established a simian-human immunodeficiency virus (SHIV) infection model in neonatal macaques that mimics intrapartum mucosal virus exposure (T. W. Baba et a ... Full text Link to item Cite

Passive immunization against oral AIDS virus transmission: an approach to prevent mother-to-infant HIV-1 transmission?

Journal Article J Med Primatol · August 2001 To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T ... Full text Link to item Cite

Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies.

Journal Article Transfus Clin Biol · August 2001 Neonatal macaques were completely protected against oral challenge with SHIV-vpu+, a simian-human immunodeficiency virus that encodes the envelope gene of a laboratory-adapted HIV strain, by pre- and post-natal treatment with a triple combination of human ... Full text Link to item Cite

Induction of neutralizing antibodies and gag-specific cellular immune responses to an R5 primary isolate of human immunodeficiency virus type 1 in rhesus macaques.

Journal Article J Virol · July 2001 The ability to generate antibodies that cross-neutralize diverse primary isolates is an important goal for human immunodeficiency virus type 1 (HIV-1) vaccine development. Most of the candidate HIV-1 vaccines tested in humans and nonhuman primates have fai ... Full text Link to item Cite

Enhanced avidity maturation of antibody to human immunodeficiency virus envelope: DNA vaccination with gp120-C3d fusion proteins.

Journal Article AIDS Res Hum Retroviruses · June 10, 2001 DNA vaccination can elicit both humoral and cellular immune responses and can confer protection against several pathogens. However, DNA vaccines expressing the envelope (Env) protein of human immunodeficiency virus (HIV) have been relatively ineffective at ... Full text Link to item Cite

Reduction of simian-human immunodeficiency virus 89.6P viremia in rhesus monkeys by recombinant modified vaccinia virus Ankara vaccination.

Journal Article J Virol · June 2001 Since cytotoxic T lymphocytes (CTLs) are critical for controlling human immunodeficiency virus type 1 (HIV-1) replication in infected individuals, candidate HIV-1 vaccines should elicit virus-specific CTL responses. In this report, we study the immune resp ... Full text Link to item Cite

Vaccine-elicited V3 loop-specific antibodies in rhesus monkeys and control of a simian-human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate envelope.

Journal Article J Virol · May 2001 Vaccine-elicited antibodies specific for the third hypervariable domain of the surface gp120 of human immunodeficiency virus type 1 (HIV-1) (V3 loop) were assessed for their contribution to protection against infection in the simian-human immunodeficiency ... Full text Link to item Cite

Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine.

Journal Article Science · April 6, 2001 Heterologous prime/boost regimens have the potential for raising high levels of immune responses. Here we report that DNA priming followed by a recombinant modified vaccinia Ankara (rMVA) booster controlled a highly pathogenic immunodeficiency virus challe ... Full text Link to item Cite

Polyvalent envelope glycoprotein vaccine elicits a broader neutralizing antibody response but is unable to provide sterilizing protection against heterologous Simian/human immunodeficiency virus infection in pigtailed macaques.

Journal Article J Virol · March 2001 The great difficulty in eliciting broadly cross-reactive neutralizing antibodies (NAbs) against human immunodeficiency virus type 1 (HIV-1) isolates has been attributed to several intrinsic properties of their viral envelope glycoprotein, including its com ... Full text Link to item Cite

QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans.

Journal Article Vaccine · February 28, 2001 Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization. The QS-21 was admini ... Full text Link to item Cite

Cellular and humoral immune responses to a canarypox vaccine containing human immunodeficiency virus type 1 Env, Gag, and Pro in combination with rgp120.

Other J Infect Dis · February 15, 2001 Elicitation of both memory cytotoxic T cell responses and human immunodeficiency virus (HIV)-neutralizing antibodies are desirable characteristics of an HIV vaccine regimen. We studied a combination vaccine regimen consisting of a canarypox (CP) vector con ... Full text Link to item Cite

Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140.

Journal Article J Virol · January 2001 The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linke ... Full text Link to item Cite

In vivo attenuation of simian immunodeficiency virus by disruption of a tyrosine-dependent sorting signal in the envelope glycoprotein cytoplasmic tail.

Journal Article J Virol · January 2001 Attenuated simian immunodeficiency viruses (SIVs) have been described that produce low levels of plasma virion RNA and exhibit a reduced capacity to cause disease. These viruses are particularly useful in identifying viral determinants of pathogenesis. In ... Full text Link to item Cite

Immunization with recombinant canarypox vectors expressing membrane-anchored glycoprotein 120 followed by glycoprotein 160 boosting fails to generate antibodies that neutralize R5 primary isolates of human immunodeficiency virus type 1.

Journal Article AIDS Res Hum Retroviruses · December 10, 2000 Antibodies generated by candidate HIV-1 vaccines in a phase I clinical trial were assessed for neutralizing activity with a panel of eight well-characterized, genetically diverse clade B primary isolates having an R5 phenotype. The vaccines consisted of on ... Full text Link to item Cite

Effective induction of simian immunodeficiency virus-specific systemic and mucosal immune responses in primates by vaccination with proviral DNA producing intact but noninfectious virions.

Journal Article J Virol · November 2000 We report a pilot evaluation of a DNA vaccine producing genetically inactivated simian immunodeficiency virus (SIV) particles in primates, with a focus on eliciting mucosal immunity. Our results demonstrate that DNA vaccines can be used to stimulate strong ... Full text Link to item Cite

Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination.

Journal Article Science · October 20, 2000 With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 ... Full text Link to item Cite

Cytokine profiles in seronegative volunteers immunized with a recombinant canarypox and gp120 prime-boost HIV-1 vaccine. NIAID AIDS Vaccine Evaluation Group.

Other AIDS · July 7, 2000 OBJECTIVES: To study memory T cell proliferative responses and cytokine profiles induced in HIV-1 seronegative volunteers immunized with a live recombinant canarypox vector expressing HIV-1 antigens (ALVAC-HIV) and boosted with a recombinant gp120 subunit ... Full text Link to item Cite

Linkage of the CCR5 Delta 32 mutation with a functional polymorphism of CD45RA.

Journal Article J Immunol · July 1, 2000 A 32-bp deletion in CCR5 (CCR5 Delta 32) confers to PBMC resistance to HIV-1 isolates that use CCR5 as a coreceptor. To study this mutation in T cell development, we have screened 571 human thymus tissues for the mutation. We identified 72 thymuses (12.6%) ... Full text Link to item Cite

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Journal Article AIDS Res Hum Retroviruses · June 10, 2000 Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp ... Full text Link to item Cite

Passive infusion of immune serum into simian immunodeficiency virus-infected rhesus macaques undergoing a rapid disease course has minimal effect on plasma viremia.

Journal Article Virology · April 25, 2000 Antibody responses are often considered to play only a limited role in controlling viremia during chronic infections with human or simian immunodeficiency virus (SIV). We investigated this by determining the effect of passively infused antibody on plasma v ... Full text Link to item Cite

Augmentation of immune responses to HIV-1 and simian immunodeficiency virus DNA vaccines by IL-2/Ig plasmid administration in rhesus monkeys.

Journal Article Proc Natl Acad Sci U S A · April 11, 2000 The potential utility of plasmid DNA as an HIV-1 vaccination modality currently is an area of active investigation. However, recent studies have raised doubts as to whether plasmid DNA alone will elicit immune responses of sufficient magnitude to protect a ... Full text Link to item Cite

Recombinant modified vaccinia virus ankara expressing the surface gp120 of simian immunodeficiency virus (SIV) primes for a rapid neutralizing antibody response to SIV infection in macaques.

Journal Article J Virol · March 2000 Neutralizing antibodies were assessed before and after intravenous challenge with pathogenic SIVsmE660 in rhesus macaques that had been immunized with recombinant modified vaccinia virus Ankara expressing one or more simian immunodeficiency virus gene prod ... Full text Link to item Cite

Induction of antibodies in guinea pigs and rhesus monkeys against the human immunodeficiency virus type 1 envelope: neutralization of nonpathogenic and pathogenic primary isolate simian/human immunodeficiency virus strains.

Journal Article J Virol · January 2000 We have compared the abilities of human immunodeficiency virus type 1 (HIV-1) envelope V3 peptides and recombinant gp120 to induce antibodies that neutralize simian/human immunodeficiency viruses (SHIVs). SHIV-89.6 is a nonpathogenic SHIV that expresses th ... Full text Link to item Cite

HIV vaccine development at Duke University Medical Center.

Journal Article Immunol Res · 2000 With the AIDS epidemic continuing to spread throughout the world, development of a safe, practical, and effective HIV vaccine is a national priority. HIV vaccine research efforts are currently targeted towards design of HIV immunogens that induce both cell ... Full text Link to item Cite

Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles.

Journal Article J Virol · January 2000 Vaccine vectors derived from Venezuelan equine encephalitis virus (VEE) that expressed simian immunodeficiency virus (SIV) immunogens were tested in rhesus macaques as part of the effort to design a safe and effective vaccine for human immunodeficiency vir ... Full text Link to item Cite

DNA priming and recombinant pox virus boosters for an AIDS vaccine.

Journal Article Dev Biol (Basel) · 2000 Eight different protocols for immunization have been compared for the ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming f ... Link to item Cite

Characterization of primary isolate-like variants of simian-human immunodeficiency virus.

Journal Article J Virol · December 1999 Several different strains of simian-human immunodeficiency virus (SHIV) that contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) strains or primary isolates of human immunodeficiency virus type 1 (HIV-1) are now available. One of the ad ... Full text Link to item Cite

A human anti-HIV autoantibody enhances EBV transformation and HIV infection.

Journal Article Clin Immunol · December 1999 A highly specific, human IgG mAb, F223, which reacts with both HIV-1-infected cells and uninfected lymphoid cells, has been derived. F223 reacts with gp120 but fails to neutralize viral infection. The antibody does enhance HIV-1 infection in a complement-d ... Full text Link to item Cite

Primary isolate neutralization by HIV type 1-infected patient sera in the era of highly active antiretroviral therapy.

Journal Article AIDS Res Hum Retroviruses · November 20, 1999 Sera from highly selected HIV-1-positive patients are known to have the ability to neutralize a diverse array of primary isolates of HIV-1. The human osteosarcoma cell line that expresses CD4 and chemokine receptors (GHOST cells) was adapted to study HIV-1 ... Full text Link to item Cite

Role of immune responses against the envelope and the core antigens of simian immunodeficiency virus SIVmne in protection against homologous cloned and uncloned virus challenge in Macaques.

Journal Article J Virol · October 1999 We previously showed that envelope (gp160)-based vaccines, used in a live recombinant virus priming and subunit protein boosting regimen, protected macaques against intravenous and intrarectal challenges with the homologous simian immunodeficiency virus SI ... Full text Link to item Cite

Protection by live, attenuated simian immunodeficiency virus against heterologous challenge.

Journal Article J Virol · October 1999 We examined the ability of a live, attenuated deletion mutant of simian immunodeficiency virus (SIV), SIVmac239Delta3, which is missing nef and vpr genes, to protect against challenge by heterologous strains SHIV89.6p and SIVsmE660. SHIV89.6p is a pathogen ... Full text Link to item Cite

Postexposure immunoprophylaxis of primary isolates by an antibody to HIV receptor complex.

Journal Article Proc Natl Acad Sci U S A · August 31, 1999 mAb B4 is a monoclonal antibody directed against HIV receptor complex. The antibody had broad neutralizing activity against HIV and provided postexposure prophylaxis to hu-peripheral blood leukocyte (PBL)-severe combined immunodeficient mice and chimpanzee ... Full text Link to item Cite

Combined systemic and mucosal immunization with microsphere-encapsulated inactivated simian immunodeficiency virus elicits serum, vaginal, and tracheal antibody responses in female rhesus macaques.

Journal Article AIDS Res Hum Retroviruses · August 10, 1999 We determined the efficacy of immunization with microsphere-encapsulated whole inactivated simian immunodeficiency virus (SIV) by combined systemic and mucosal administration to protect female rhesus macaques against vaginal challenge with homologous rhesu ... Full text Link to item Cite

A canarypox vaccine expressing multiple human immunodeficiency virus type 1 genes given alone or with rgp120 elicits broad and durable CD8+ cytotoxic T lymphocyte responses in seronegative volunteers.

Journal Article J Infect Dis · August 1999 Induction of CD8+ cytotoxic T cells is considered one of the important correlates for the protective efficacy of candidate human immunodeficiency virus type 1 (HIV-1) vaccines. To induce CD8+ cytotoxic T lymphocytes (CTLs) along with neutralizing antibody ... Full text Link to item Cite

Epitope insertion into variable loops of HIV-1 gp120 as a potential means to improve immunogenicity of viral envelope protein.

Journal Article Vaccine · July 16, 1999 We report on the properties of a set of HIV-1 IIIB Env mutants carrying a linear gp41 epitope insertion (LLELDKWASL) in the V1, V2, V3 or V4 variable loop. Insertion of the epitope, which is defined by the HIV-1 neutralizing MAb 2F5, was well tolerated in ... Full text Link to item Cite

Induction of mucosal antibody responses by microsphere-encapsulated formalin-inactivated simian immunodeficiency virus in a male urethral challenge model.

Journal Article Vaccine · July 16, 1999 Male rhesus macaques were immunized mucosally with microsphere-encapsulated formalin-inactivated simian immunodeficiency virus (SIV) particles in a test of immunogenicity and protection against mucosal SIV challenge. Tracheal boosting of animals that had b ... Full text Link to item Cite

Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection.

Journal Article J Virol · July 1999 Human immunodeficiency virus type 1 (HIV-1)-specific immune responses over the course of rapidly progressive infection are not well defined. Detailed longitudinal analyses of neutralizing antibodies, lymphocyte proliferation, in vivo-activated and memory c ... Full text Link to item Cite

Neutralizing antibody responses in Africa green monkeys naturally infected with simian immunodeficiency virus (SIVagm).

Journal Article J Med Primatol · June 1999 This study assessed the magnitude and cross-reactivity of the neutralizing antibody response generated by natural SIV infection in wild-caught African green monkeys. Neutralizing antibodies of variable potency, sometimes exceeding a titer of 1:1,000, were ... Full text Link to item Cite

Highly attenuated vaccine strains of simian immunodeficiency virus protect against vaginal challenge: inverse relationship of degree of protection with level of attenuation.

Journal Article J Virol · June 1999 Three different deletion mutants of simian immunodeficiency virus (SIV) that vary in their levels of attenuation were tested for the ability to protect against mucosal challenge with pathogenic SIV. Four female rhesus monkeys were vaccinated by intravenous ... Full text Link to item Cite

Neutralization escape in human immunodeficiency virus type 1-infected long-term nonprogressors.

Journal Article J Infect Dis · May 1999 Neutralization-escape variants of human immunodeficiency virus type 1 (HIV-1) were sought in persons who had persistent low virus loads and who remained asymptomatic for at least 12-16 years of infection without antiretroviral therapy. Viruses were isolate ... Full text Link to item Cite

Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations.

Journal Article Nat Med · May 1999 Eight different protocols were compared for their ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombina ... Full text Link to item Cite

Protection of macaques against intrarectal infection by a combination immunization regimen with recombinant simian immunodeficiency virus SIVmne gp160 vaccines.

Journal Article J Virol · April 1999 We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against intravenous challenge by the cloned homologous virus E11S but that this protection was only partially effect ... Full text Link to item Cite

Rapid and slow progressors differ by a single MHC class I haplotype in a family of MHC-defined rhesus macaques infected with SIV.

Journal Article Immunol Lett · March 1999 Highly polymorphic HLA class I molecules may influence rates of disease progression of HIV-infected individuals. Recent evidence suggests that individuals who mount vigorous CTL responses to multiple HIV-1 epitopes have reduced viral loads, and survive lon ... Full text Link to item Cite

Protection from pathogenic SIV challenge using multigenic DNA vaccines.

Journal Article Immunol Lett · March 1999 To assess DNA immunization as a strategy for protecting against HIV infection in humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine challenge model with moderate pathogenic potential. We compared the efficacy of DNA immunization alone ... Full text Link to item Cite

Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes.

Journal Article Science · February 5, 1999 Clinical evidence suggests that cellular immunity is involved in controlling human immunodeficiency virus-1 (HIV-1) replication. An animal model of acquired immune deficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)-infected rhesus monkey, ... Full text Link to item Cite

Effect of complement consumption by cobra venom factor on the course of primary infection with simian immunodeficiency virus in rhesus monkeys.

Journal Article AIDS Res Hum Retroviruses · January 20, 1999 Cobra venom factor (CVF)-induced consumption of complement proteins was used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (SIVmac) infection in rhesus monkeys. Repeated administration ... Full text Link to item Cite

Limited breadth of the protective immunity elicited by simian immunodeficiency virus SIVmne gp160 vaccines in a combination immunization regimen.

Journal Article J Virol · January 1999 We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against an intravenous challenge by the cloned homologous virus, E11S. In this study, we confirmed this observation ... Full text Link to item Cite

Immunization against SIVmne in macaques using multigenic DNA vaccines.

Journal Article J Med Primatol · 1999 All structural and regulatory genes of SIVmne were cloned into mammalian expression vectors to optimize expression in vitro and immunogenicity in mice. Macaca fascicularis were immunized four times with plasmid DNA (n = 4), or two DNA priming inoculations ... Full text Link to item Cite

Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group.

Journal Article AIDS · December 24, 1998 OBJECTIVE: To determine the ability of live attenuated canarypox virus expressing HIV antigens to induce CD8+ cytotoxic T-cell responses and to prime for neutralizing antibody responses to boosting with purified recombinant gp120 subunit vaccine. DESIGN: A ... Full text Link to item Cite

Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting.

Journal Article J Virol · November 1998 DNA vaccination is an effective means of eliciting strong antibody responses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing antibody responses to human immunodeficiency viru ... Full text Link to item Cite

Determinants of disease in the simian immunodeficiency virus-infected rhesus macaque: characterizing animals with low antibody responses and rapid progression.

Journal Article J Gen Virol · October 1998 Clinical and laboratory markers of simian immunodeficiency virus (SIV) infection were studied during the first 3 months after intravenous inoculation of rhesus macaques. Virus-binding serum antibody titres were correlated strongly with disease progression ... Full text Link to item Cite

Functional and molecular characterization of human monoclonal antibody reactive with the immunodominant region of HIV type 1 glycoprotein 41.

Journal Article AIDS Res Hum Retroviruses · September 20, 1998 The immunoreactivity, functional activity, and molecular features of a human monoclonal antibody (HMAb), F240, from an HIV-1-infected individual have been studied. Flow cytometric analysis demonstrated that F240 is reactive with cells infected with a broad ... Full text Link to item Cite

Rhesus macaques that become systemically infected with pathogenic SHIV 89.6-PD after intravenous, rectal, or vaginal inoculation and fail to make an antiviral antibody response rapidly develop AIDS.

Journal Article J Acquir Immune Defic Syndr Hum Retrovirol · September 1, 1998 A new simian-human immunodeficiency virus (SHIV) stock (SHIV 89.6-PD), derived from plasma of a rhesus macaque used for in vivo serial passage of virulence-attenuated SHIV 89.6, produces systemic infection after intravenous, intravaginal, or intrarectal in ... Full text Link to item Cite

Temporal analyses of virus replication, immune responses, and efficacy in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine.

Journal Article J Virol · September 1998 Despite evidence that live, attenuated simian immunodeficiency virus (SIV) vaccines can elicit potent protection against pathogenic SIV infection, detailed information on the replication kinetics of attenuated SIV in vivo is lacking. In this study, we meas ... Full text Link to item Cite

Neutralizing antibodies in sera from macaques immunized with attenuated simian immunodeficiency virus.

Journal Article J Virol · August 1998 Infection with attenuated simian immunodeficiency virus (SIV) in rhesus macaques has been shown to raise antibodies capable of neutralizing an animal challenge stock of primary SIVmac251 in CEMx174 cells that correlate with resistance to infection after ex ... Full text Link to item Cite

Viral genetic evolution in macaques infected with molecularly cloned simian immunodeficiency virus correlates with the extent of persistent viremia.

Journal Article J Virol · August 1998 Genetic evolution of the simian immunodeficiency virus (SIV) envelope glycoprotein was evaluated in a group of six macaques (Macaca nemestrina) infected with the molecularly cloned, moderately pathogenic SIVsm62d. The extent of envelope evolution was subse ... Full text Link to item Cite

Recombinant vaccine-induced protection against the highly pathogenic simian immunodeficiency virus SIV(mac251): dependence on route of challenge exposure.

Journal Article J Virol · May 1998 Vaccine protection from infection and/or disease induced by highly pathogenic simian immunodeficiency virus (SIV) strain SIV(mac251) in the rhesus macaque model is a challenging task. Thus far, the only approach that has been reported to protect a fraction ... Full text Link to item Cite

Passive immunization of newborn rhesus macaques prevents oral simian immunodeficiency virus infection.

Journal Article J Infect Dis · May 1998 To determine if passively acquired antiviral antibodies modulate virus transmission and disease progression in human pediatric AIDS, the potential of pre- and postexposure passive immunization with hyperimmune serum to prevent oral simian immunodeficiency ... Full text Link to item Cite

Neutralizing antibodies in sera from macaques infected with chimeric simian-human immunodeficiency virus containing the envelope glycoproteins of either a laboratory-adapted variant or a primary isolate of human immunodeficiency virus type 1.

Journal Article J Virol · April 1998 The magnitude and breadth of neutralizing antibodies raised in response to infection with chimeric simian-human immunodeficiency virus (SHIV) in rhesus macaques were evaluated. Infection with either SHIV-HXB2, SHIV-89.6, or SHIV-89.6PD raised high-titer ne ... Full text Link to item Cite

Oral SIV, SHIV, and HIV type 1 infection.

Journal Article AIDS Res Hum Retroviruses · April 1998 Several strains of simian immunodeficiency virus (SIV), including uncloned and molecularly cloned SIV strains, can cross intact mucosal surfaces after oral exposure in both adult and neonatal rhesus macaques, resulting in viremia and disease. Cell-free SIV ... Link to item Cite

Evidence that antibody-mediated neutralization of human immunodeficiency virus type 1 by sera from infected individuals is independent of coreceptor usage.

Journal Article J Virol · March 1998 Human immunodeficiency virus type 1 (HIV-1) uses a variety of chemokine receptors as coreceptors for virus entry, and the ability of the virus to be neutralized by antibody may depend on which coreceptors are used. In particular, laboratory-adapted variant ... Full text Link to item Cite

Immunogenicity of DNA vaccines expressing human immunodeficiency virus type 1 envelope glycoprotein with and without deletions in the V1/2 and V3 regions.

Journal Article AIDS Res Hum Retroviruses · January 20, 1998 DNA vaccines that express the human immunodeficiency virus type 1 HXB-2 envelope glycoprotein (Env) with or without deletions of the major variable regions V1/V2 and V3 were tested for the ability to raise enzyme-linked immunosorbent assay (ELISA) and neut ... Full text Link to item Cite

Simian immunodeficiency virus (SIV) envelope-specific Fabs with high-level homologous neutralizing activity: recovery from a long-term-nonprogressor SIV-infected macaque.

Journal Article J Virol · January 1998 An antibody phage display library was constructed from RNA extracted from lymph node cells of a simian immunodeficiency virus (SIV)-infected long-term-nonprogressor macaque. Seven gp120-reactive Fabs were obtained by selection of the library against SIV mo ... Full text Link to item Cite

Vaccine evaluation studies of replication-defective SIVsmB7.

Journal Article Cell Mol Biol (Noisy-le-grand) · November 1997 Non-infectious virus-like particles of SIVsmB7 that expresses env and gag gene products but are defective in pol and vpx/vpr were assessed for their ability to induce protective immunity against infection with pathogenic SIVsmE660 in rhesus macaques. Anima ... Link to item Cite

Neutralizing antibody responses to human immunodeficiency virus type 1 in primary infection and long-term-nonprogressive infection.

Journal Article J Infect Dis · October 1997 The role of neutralizing antibodies in human immunodeficiency virus type 1 (HIV-1) infection is poorly understood and was assessed by evaluating responses at different stages of infection. Undiluted sera from long-term nonprogressors (LTNP) had broad neutr ... Full text Link to item Cite

Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination.

Journal Article Proc Natl Acad Sci U S A · August 19, 1997 It is generally thought that an effective vaccine to prevent HIV-1 infection should elicit both strong neutralizing antibody and cytotoxic T lymphocyte responses. We recently demonstrated that potent, boostable, long-lived HIV-1 envelope (Env)-specific cyt ... Full text Link to item Cite

Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting.

Journal Article Virology · April 14, 1997 HIV-1 envelopes from two series of primary isolates (from Swedish patients 5 and 6), from JR-FL and BaL (prototypic monocyte/macrophage tropic viruses) and from HXB-2 (a prototypic T-cell-line-adapted virus), have been screened for their ability to elicit ... Full text Link to item Cite

Antibody-mediated neutralization of primary isolates of human immunodeficiency virus type 1 in peripheral blood mononuclear cells is not affected by the initial activation state of the cells.

Journal Article J Virol · March 1997 Antibody-mediated neutralization of human immunodeficiency virus type 1 (HIV-1) was evaluated with primary isolates and sera from infected individuals, using human peripheral blood mononuclear cells (PBMC) activated with phytohemagglutinin 1 day after viru ... Full text Link to item Cite

A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3.

Journal Article J Virol · February 1997 An infectious molecular clone of simian immunodeficiency virus SIVsm was derived from a biological isolate obtained late in disease from an immunodeficient rhesus macaque (E543) with SIV-induced encephalitis. The molecularly cloned virus, SIVsmE543-3, repl ... Full text Link to item Cite

Immunization with HIV-1 gp160 by the ''prime and boost'' regimen protects macaques against SHIV HXBc2 challenge

Conference VACCINES 97 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES · January 1, 1997 Link to item Cite

A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3

Conference VACCINES 97 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES · January 1, 1997 Link to item Cite

Neutralizing and infection-enhancing antibody responses do not correlate with the differential pathogenicity of SIVmac239delta3 in adult and infant rhesus monkeys.

Journal Article J Immunol · December 15, 1996 Variants of SIV containing a deletion in the nef gene are attenuated in adult macaques, where they provide protection from challenge with pathogenic SIV, but the mechanism of protection remains unknown. One of these attenuated variants carrying deletions i ... Link to item Cite

Complement-activating antibodies in sera from infected individuals and vaccinated volunteers that target human immunodeficiency virus type 1 to complement receptor type 1 (CR1, CD35).

Journal Article Virology · December 1, 1996 Complement receptor type 1 (CR1) plays a central role in clearing immune complexes from the circulation and probably contributes to the retention of immune complexes on the surface of follicular dendritic cells. Virus-specific, complement-activating antibo ... Full text Link to item Cite

The V3 domain of SIVmac251 gp120 contains a linear neutralizing epitope.

Journal Article Virology · October 15, 1996 Antisera to 21 synthetic peptides containing hydrophilic sequences of simian immunodeficiency virus strain mac251 (SIVmac251) gp120 and gp32 were tested for the ability to neutralize SIVmac251. Goat antisera raised to peptides SP-1 and SP-1V containing the ... Full text Link to item Cite

Simian immunodeficiency virus DNA vaccine trial in macaques.

Journal Article J Virol · June 1996 An experimental vaccine consisting of five DNA plasmids expressing different combinations and forms of simian immunodeficiency virus-macaque (SIVmac) proteins has been evaluated for the ability to protect against a highly pathogenic uncloned SIVmac251 chal ... Full text Link to item Cite

Vaccine protection by a triple deletion mutant of simian immunodeficiency virus.

Journal Article J Virol · June 1996 Twelve rhesus monkeys were vaccinated with SIVmac316 delta nef (lacking nef sequences), and 12 were vaccinated with SIVmac239 delta3 (lacking nef, vpr, and upstream sequences in U3). SIVmac316 and SIVmac239 differ by only eight amino acids in the envelope; ... Full text Link to item Cite

Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara.

Journal Article J Virol · June 1996 The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia ... Full text Link to item Cite

An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys.

Journal Article J Virol · May 1996 To explore the roles played by specific human immunodeficiency virus type 1 (HIV-1) genes in determining the in vivo replicative capacity of AIDS viruses, we have examined the replication kinetics and virus-specific immune responses in rhesus monkeys follo ... Full text Link to item Cite

Human immunodeficiency virus type 1 infection despite prior immunization with a recombinant envelope vaccine regimen.

Journal Article Proc Natl Acad Sci U S A · April 30, 1996 With efforts underway to develop a preventive human immunodeficiency virus type 1 (HIV-1) vaccine, it remains unclear which immune responses are sufficient to protect against infection and whether prior HIV-1 immunity can alter the subsequent course of HIV ... Full text Link to item Cite

DNA vaccines.

Journal Article AIDS Res Hum Retroviruses · March 20, 1996 Full text Link to item Cite

Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long-term nonprogressors.

Journal Article J Infect Dis · January 1996 Serum antibodies from human immunodeficiency virus type 1 (HIV-1)-infected long-term non-progressors (LTNPs) and non-LTNPs were evaluated for virus neutralization and infection enhancement in vitro. Sera from LTNPs had higher average titers of neutralizing ... Full text Link to item Cite

Role of complement in HIV and SIV pathogenesis and immunity

Conference SYMPOSIUM IN IMMUNOLOGY V · January 1, 1996 Link to item Cite

Simian immunodeficiency virus DNA vaccine trial in macaques.

Journal Article Ann N Y Acad Sci · November 27, 1995 Full text Link to item Cite

Influence of heavy chain constant regions on antigen binding and HIV-1 neutralization by a human monoclonal antibody.

Journal Article J Immunol · October 1, 1995 F105, a neutralizing IgG1 kappa human mAb, is reactive with a discontinuous epitope within the gp120 CD4 binding site. Because isotype usage may affect Ab function, we examined the effect of isotype on Ag/Ab interactions and HIV-1 neutralization. An IgG3 k ... Link to item Cite

Studies of complement-activating antibodies in the SIV/macaque model of acute primary infection and vaccine protection.

Journal Article AIDS Res Hum Retroviruses · August 1995 Questions regarding the potential impact of complement-activating antibodies on lentivirus pathogenesis and vaccine development were addressed in the SIV/macaque model by evaluating sera for activity related to complement-mediated, antibody-dependent enhan ... Full text Link to item Cite

A macaque adherent cell line that expresses human CD4 is susceptible to SIV: utility for assessing neutralizing antibody.

Journal Article J Virol Methods · May 1995 A macaque CD4 + adherent cell line was generated by stable expression of the human CD4 gene in a rhesus macaque mammary tumor cell line, CMMT. The resulting cell line CMMT/CD4 expressed surface CD4 and was sensitive to infection by a wide range of isolates ... Full text Link to item Cite

Studies in subjects with long-term nonprogressive human immunodeficiency virus infection.

Journal Article N Engl J Med · January 26, 1995 BACKGROUND: In a small percentage of persons infected with human immunodeficiency virus type 1 (HIV-1), there is no progression of disease and CD4+ T-cell counts remain stable for many years. Studies of the histopathological, virologic, and immunologic cha ... Full text Link to item Cite

WHAT IS THE FATE OF COMPLEMENT-OPSONIZED HIV

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · January 1, 1995 Link to item Cite

SIV PATHOGENESIS DURING ONTOGENY - THE VIRUS THRESHOLD HYPOTHESIS

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · January 1, 1995 Link to item Cite