Scholars@Duke
Celia Crane LaBranche

Celia Crane LaBranche

Associate Professor Emeritus
Surgery, Surgical Sciences
celia.labranche@duke.edu
1042 Steinbeck Dr, Durham, NC 27703
205 Surg Oncol Res Fac, 915 S. LaSalle Street, Durham, NC 27710

Selected Publications

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

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

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

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

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

Journal Article J Virol · June 8, 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 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

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

The Glycan Hole Area of HIV-1 Envelope Trimers Contributes Prominently to the Induction of Autologous Neutralization.

Journal Article Journal of virology · January 2022 The human immunodeficiency virus type 1 (HIV-1) trimeric envelope glycoprotein (Env) is heavily glycosylated, creating a dense glycan shield that protects the underlying peptidic surface from antibody recognition. The absence of conserved glycans, due to m ... Full text 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

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

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

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

Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2.

Journal Article Adv Ther (Weinh) · April 2021 Hexavalent sulfoglycodendrimers (SGDs) are synthesized as mimics of host cell heparan sulfate proteoglycans (HSPGs) to inhibit the early stages in viral binding/entry of HIV-1 and SARS-CoV-2. Using an HIV neutralization assay, the most promising of the sev ... 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

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

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

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

An Efficient Microwave-Mediated Synthesis of Hexavalent Sialic Acid Sulfoglycodendrimers as Potential Anti-HIV Agents.

Journal Article ACS Appl Polym Mater · November 13, 2020 A series of four sialic acid-containing hexavalent sulfoglycodendrimers (SGDs) were synthesized in excellent yields using an efficient strategy involving multiple microwave-mediated reactions. Four sugars, sialic acid, and the dimer through tetramer of α-2 ... Full text Link to item Cite

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

Journal Article Journal of virology · November 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 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

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

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

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

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

Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help.

Journal Article Nat Commun · May 21, 2020 The inherent molecular complexity of human pathogens requires that mammals evolved an adaptive immune system equipped to handle presentation of non-conventional MHC ligands derived from disease-causing agents, such as HIV-1 envelope (Env) glycoprotein. Her ... 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

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

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

Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.

Journal Article J Virol · February 28, 2020 Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell int ... 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

Therapeutic vaccination with IDLV-SIV-Gag results in durable viremia control in chronically SHIV-infected macaques.

Journal Article NPJ Vaccines · 2020 Despite incredible scientific efforts, there is no cure for HIV infection. While antiretroviral treatment (ART) can help control the virus and prevent transmission, it cannot eradicate HIV from viral reservoirs established before the initiation of therapy. ... 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

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

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

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

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

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

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

PI-6 Construction and analysis of V3 glycopeptide antigens for HIV-1 vaccine design

Conference JAIDS Journal of Acquired Immune Deficiency Syndromes · April 2019 The heavy glycosylation on HIV-1 envelope protein (Env) plays an important role in viral evasion and is critical for the viral plasticity and diversity in the circulating strains. The discovery of a new class of broadly neutralizing antibodies (bnA ... Full text 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Corrigendum

Journal Article Human Vaccines & Immunotherapeutics · April 2, 2016 Full text 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

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

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

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

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

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

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

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

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

Journal Article Retrovirology · September 2015 BackgroundPresenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation.FindingsWe describe ferritin-based protein nanoparticles that display multiple copies of native-like HIV-1 envelope ... Full text 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

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

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

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

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

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

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 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

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

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

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

Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies.

Journal Article Cell · July 31, 2014 Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here, we study ... 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

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

Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV

Journal Article Nature · January 1, 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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Evaluation of the synthesis of sialic acid-PAMAM glycodendrimers without the use of sugar protecting groups, and the anti-HIV-1 properties of these compounds.

Journal Article Bioconjug Chem · October 19, 2011 A study was undertaken to evaluate the feasibility of synthesizing six sialic acid-PAMAM glycodendrimers using unprotected sialic acid in as few as 1-4 steps using two different reaction pathways, and to assess the sulfated derivatives for anti-HIV activit ... 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 type 1 from a patient with baseline resistance to CCR5 antagonists uses drug-bound receptor for entry.

Journal Article AIDS Res Hum Retroviruses · January 2010 CCR5 antagonists are a new class of antiretroviral drugs that block viral entry by disrupting interactions between the viral envelope (Env) glycoprotein and coreceptor. During the CCR100136 (EPIC) Phase IIb study of the CCR5 antagonist aplaviroc (APL) in t ... Full text Link to item Cite

Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic HIV from the plasma of drug-naive individuals.

Journal Article AIDS · July 31, 2008 OBJECTIVE: HIV-1 utilizes CD4 and either chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4) to gain entry into host cells. Small molecule CCR5 antagonists are currently being developed for the treatment of HIV-1 infection ... Full text Link to item Cite

Conformation of gp120 determines the sensitivity of HIV-1 DH012 to the entry inhibitor IC9564.

Journal Article Virology · July 1, 2004 The HIV-1 envelope glycoprotein gp120 is the key determinant for the anti-HIV-1 entry activity of IC9564. A T198P mutation in the gp120 of the HIV-1 primary isolate, DH012, drastically increases IC9564 sensitivity, which can be reversed by growing the viru ... Full text Link to item Cite

Mutations that destabilize the gp41 core are determinants for stabilizing the simian immunodeficiency virus-CPmac envelope glycoprotein complex.

Journal Article J Biol Chem · April 12, 2002 The human and simian immunodeficiency viruses (HIV and SIV) envelope glycoprotein consists of a trimer of two noncovalently and weakly associated subunits, gp120 and gp41. Upon binding of gp120 to cellular receptors, this labile native envelope complex und ... Full text Link to item Cite

Relationships between CD4 independence, neutralization sensitivity, and exposure of a CD4-induced epitope in a human immunodeficiency virus type 1 envelope protein.

Journal Article J Virol · June 2001 A CD4-independent version of the X4 human immunodeficiency virus type 1 (HIV-1) HXBc2 envelope (Env) protein, termed 8x, mediates infection of CD4-negative, CXCR4-positive cells, binds directly to CXCR4 in the absence of CD4 due to constitutive exposure of ... Full text Link to item Cite

HIV fusion and its inhibition.

Journal Article Antiviral Res · May 2001 Full text Link to item Cite

Differential CD4/CCR5 utilization, gp120 conformation, and neutralization sensitivity between envelopes from a microglia-adapted human immunodeficiency virus type 1 and its parental isolate.

Journal Article J Virol · April 2001 Human immunodeficiency virus type 1 (HIV-1) infects and induces syncytium formation in microglial cells from the central nervous system (CNS). A primary isolate (HIV-1(BORI)) was sequentially passaged in cultured microglia, and the isolate recovered (HIV-1 ... Full text Link to item Cite

Determinants of CD4 independence for a human immunodeficiency virus type 1 variant map outside regions required for coreceptor specificity.

Journal Article J Virol · December 1999 Although infection by human immunodeficiency virus (HIV) typically requires an interaction between the viral envelope glycoprotein (Env), CD4, and a chemokine receptor, CD4-independent isolates of HIV and simian immunodeficiency virus have been described. ... Full text Link to item Cite

Stable exposure of the coreceptor-binding site in a CD4-independent HIV-1 envelope protein.

Journal Article Proc Natl Acad Sci U S A · May 25, 1999 We recently derived a CD4-independent virus from HIV-1/IIIB, termed IIIBx, which interacts directly with the chemokine receptor CXCR4 to infect cells. To address the underlying mechanism, a cloned Env from the IIIBx swarm (8x) was used to produce soluble g ... Full text Link to item Cite

CD4-independent utilization of the CXCR4 chemokine receptor by HIV-1 and HIV-2.

Journal Article J Reprod Immunol · December 1998 HIV entry is mediated by an interaction between CD4 and members of the chemokine receptor family of proteins. It is likely that CD4 induces conformational changes in the viral envelope glycoproteins that facilitate a subsequent interaction with the chemoki ... Full text Link to item Cite

An internalization signal in the simian immunodeficiency virus transmembrane protein cytoplasmic domain modulates expression of envelope glycoproteins on the cell surface.

Journal Article J Cell Biol · March 1996 A Tyr to Cys mutation at amino acid position 723 in the cytoplasmic domain of the simian immunodeficiency virus (SIV) transmembrane (TM) molecule has been shown to increase expression of envelope glycoproteins on the surface of infected cells. Here we show ... Full text Link to item Cite

A single amino acid change in the cytoplasmic domain of the simian immunodeficiency virus transmembrane molecule increases envelope glycoprotein expression on infected cells.

Journal Article J Virol · September 1995 We have described a virus termed CP-MAC, derived from the BK28 molecular clone of simian immunodeficiency virus, that was remarkable for its ability to infect Sup-T1 cells with rapid kinetics, cell fusion, and CD4 down-modulation (C. C. LaBranche, M. M. Sa ... Full text Link to item Cite

Biological, molecular, and structural analysis of a cytopathic variant from a molecularly cloned simian immunodeficiency virus.

Journal Article J Virol · September 1994 Some isolates of simian immunodeficiency virus (SIV) have been shown to infect Sup-T1 cells with slow kinetics and in the absence of cytopathic effects, including cell fusion or CD4 down-modulation (J. A. Hoxie, B. S. Haggarty, S. Bonser, J. Rackowski, H. ... Full text Link to item Cite

Deletion of carboxy-terminal residues of murine granulocyte-macrophage colony-stimulating factor results in a loss of biologic activity and altered glycosylation.

Journal Article Arch Biochem Biophys · January 1990 A deletion mutant of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) which differs in primary structure from native GM-CSF in the carboxy-terminal 11 amino acids was prepared. Four amino acid residues are mutated and the seven terminal res ... Full text Link to item Cite