Scholars@Duke
Georgia Doris Tomaras

Georgia Doris Tomaras

A. Geller Distinguished Professor for Research in Immunology
Surgery, Surgical Sciences
gdt@duke.edu
Box 104777 DUMC, Bay 47 Carmichael Bldg, 300 N. Duke St, Durham, NC 27701
300 N Duke St, Durham, NC 27701

Scholarly Works - Journal articles

Time to HIV rebound after infusion of long-acting broadly neutralising antibodies 3BNC117-LS and 10-1074-LS and analytical treatment interruption (the RIO trial): a double-blind, randomised, placebo-controlled trial.

Journal article Lancet HIV · August 2026 BACKGROUND: HIV-specific broadly neutralising antibodies (bNAbs) can maintain viral control after interrupting antiretroviral therapy (ART). We investigated the duration and efficacy of Fc-engineered long-acting bNAbs (LS-bNAbs) in maintaining ART-free HIV ... Full text Link to item Cite

Rapid and robust immune response boosting with potent, next-generation adjuvant in viral vector-primed primates.

Journal article J Virol · July 27, 2026 To identify strategies for augmenting vaccine immunogenicity, we compared a pox-protein prime-boost regimen comprising recombinant modified vaccinia virus Ankara and multimeric HIV-1 Env gp145, adjuvanted with Army Liposomal Formulation (ALF) either adsorb ... Full text Link to item Cite

In vitro recapitulation of intramuscular mRNA vaccination with naive and recall antigens using a human lymphoid follicle chip platform.

Journal article iScience · July 17, 2026 Predicting the efficacy and toxicity of mRNA vaccines remains challenging. We describe an in vitro human model that replicates immune responses to lipid nanoparticle (LNP)-based mRNA vaccines upon intramuscular injection. Vaccines are administered to human ... Full text Link to item Cite

Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, VRC07-523LS, and PGT121.414.LS infused intravenously or subcutaneously (HVTN 140/HPTN 101 part B): a phase 1, randomised trial.

Journal article Lancet HIV · July 2026 BACKGROUND: Passive immunisation with a combination of broadly neutralising monoclonal antibodies (mAbs) presents a potential HIV-1 prevention modality. This study (HVTN 140/HPTN 101) sought to evaluate PGDM1400LS (targeting V3-glycan) administered alone ( ... Full text Link to item Cite

DNA electroporation of HIV Env elicits robust T cell responses and memory B cell responses with muted serum antibody levels that can be boosted with recombinant protein.

Journal article Vaccine · April 19, 2026 Broadly neutralizing antibodies against the HIV envelope protein exhibit the potential to prevent HIV-1 acquisition, a concept demonstrated both in non-human primate (NHP) challenge models and in human clinical trials. The use of DNA for vaccination, in co ... Full text Link to item Cite

Coordinated immune response distinguishes duration of SARS-CoV-2 viral particle shedding in humans.

Journal article iScience · April 17, 2026 SARS-CoV-2 acquisition induces a spectrum of COVID-19 disease severity and duration among people. Prolonged viral antigen shedding (PVS) is defined as when a person tests positive by direct antigen tests performed a minimum of 21 days apart. It is unclear ... Full text Link to item Cite

DNA origami vaccine nanoparticles improve humoral and cellular immune responses to infectious diseases.

Journal article Nat Biomed Eng · March 11, 2026 Current SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccines have shown robust induction of neutralizing antibodies and CD4+ T cell activation; however, CD8+ responses are variable, and the duration of immunity and protection against varia ... Full text Link to item Cite

SARS-CoV-2 antibody-dependent enhancement of infection depends on antibody binding to both ACE2 and Fc receptors.

Journal article JCI Insight · February 23, 2026 Antibody-dependent enhancement (ADE) of infection is a well-described phenomenon for several viruses, including dengue, Ebola, respiratory syncytial virus, and HIV. ADE occurs when virus-antibody complexes engage Fc receptors (FcRs) and virus-specific rece ... Full text Link to item Cite

Current Approaches for Assessments of Neutralizing, Binding, and Effector Functions of Antibodies on the Path to Antibody-Mediated Prevention Strategies for HIV-1.

Journal article Curr HIV Res · 2026 Robust assay technologies and reference reagents are essential components in efforts to develop safe and effective antibody-mediated prevention strategies for HIV-1. Here, we describe current approaches used to conduct standardized assessments of neutraliz ... Full text Link to item Cite

Early rise in nasal secretory IgA associated with shorter duration of SARS-CoV-2 virus shedding in an acute infection cohort.

Journal article Front Immunol · 2026 INTRODUCTION: Understanding the role of mucosal immune responses in preventing coronavirus replication is essential for the development of broad-spectrum therapeutics and vaccines capable of interrupting transmission. Investigating the relationship between ... Full text Link to item Cite

AS01B-, MF59-, and alum-based adjuvants and HIV vaccine immunogenicity: a post-hoc cross-protocol comparison of results from HVTN 100, 107, 120, and 702.

Journal article Front Immunol · 2026 INTRODUCTION: Vaccine adjuvants are crucial in HIV vaccine development, enhancing immune responses. Immune responses generated by different adjuvanted vaccines are rarely compared directly with the same vaccine antigens. METHODS: This retrospective cross-p ... Full text Link to item Cite

Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity.

Journal article J Virol · December 23, 2025 UNLABELLED: HIV-1 continues to pose a significant global health challenge, requiring ongoing research into effective prevention and treatment strategies. Understanding the B-cell repertoire that can be engaged upon vaccination in humans is crucial for the ... Full text Link to item Cite

Hydrogel formulations for sustained-release of broadly neutralizing antibodies.

Journal article J Control Release · December 10, 2025 Sustained serum levels of broadly neutralizing antibodies (bnAbs) are crucial for effective passive immunization against infectious diseases as protection persists only while these bnAbs remain at adequate concentrations within the body. Current obstacles, ... Full text Link to item Cite

A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials.

Journal article Emerg Microbes Infect · December 2025 Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any effi ... Full text Link to item Cite

IgG and Fc Receptor Genetic Variation Associates With Functional Antibody Responses in a DNA and Protein Candidate HIV Vaccine Trial.

Journal article J Acquir Immune Defic Syndr · December 1, 2025 BACKGROUND: The HVTN108 trial evaluated the safety and immunogenicity of a DNA prime, adjuvanted protein boost HIV vaccine in the United States and South Africa. The underlying factors influencing individual variation in vaccine responsiveness are unknown. ... Full text Link to item Cite

HIV-1 envelope trimer vaccine induces sex-associated differences in antibody responses: a phase 1 clinical trial.

Journal article Nat Commun · November 21, 2025 A protective vaccine will be the most powerful instrument to reduce HIV-1 infections worldwide and help bring about a lasting end to the AIDS epidemic. The single centre, randomised, open-label, uncontrolled, phase 1 ACTHIVE-001 clinical trial (NCT03961438 ... Full text Link to item Cite

Candidate correlates of protection in the HVTN505 HIV-1 vaccine efficacy trial identified by positive-unlabeled learning.

Journal article PLoS Comput Biol · November 2025 With a goal of unveiling mechanisms by which vaccines can provide protection against HIV-1 acquisition, several studies have explored correlates of risk of HIV-1 acquisition in HVTN 505, which was a phase IIb trial conducted to assess the safety and effica ... Full text Link to item Cite

Neutralizing and binding antibodies are a correlate of risk of COVID-19 in the CoVPN 3008 study in people with HIV.

Journal article Nat Commun · October 6, 2025 People with HIV (PWH) are understudied in COVID-19 vaccine trials, leaving knowledge gaps on whether the identified immune correlates of protection also hold in PWH. CoVPN 3008 (NCT05168813) enrolled predominantly PWH and reported lower COVID-19 incidence ... Full text Open Access Link to item Cite

Qualification of a reporter virus microneutralization assay for evaluation of influenza specific antibodies in human clinical trials.

Journal article Vaccine · October 3, 2025 Neutralizing antibodies can block the entry of viruses into host cells. Next-generation influenza vaccines should stimulate the production of high levels of neutralizing antibodies capable of preventing influenza infection or reducing the severity of disea ... Full text Link to item Cite

Candidate Correlates of Protection in the HVTN505 HIV-1 Vaccine Efficacy Trial Identified by Positive-Unlabeled Learning.

Journal article medRxiv · September 7, 2025 With a goal of unveiling mechanisms by which vaccines can provide protection against HIV-1 acquisition, several studies have explored correlates of risk of HIV-1 acquisition in HVTN 505, which was a phase IIb trial conducted to assess the safety and effica ... Full text Link to item Cite

An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals.

Journal article medRxiv · August 22, 2025 UNLABELLED: Broadly neutralizing antibodies (bnAbs) that target the HIV gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand MPER bnAb precursors in monkeys ... Full text Link to item Cite

Transient regulatory T cell manipulation is limited by anti-antibody responses in HIV-1 envelope immunized rhesus macaques.

Journal article iScience · August 15, 2025 CD25+ FoxP3+ CD4+ regulatory T (Treg) cells promote immune tolerance. We studied germinal center responses and HIV-1 antibody development in rhesus macaques (RMs) immunized with sequential CH505 gp120 envelopes (Envs), with or without anti-CD25 monoclonal ... Full text Link to item Cite

Precise targeting of HIV broadly neutralizing antibody precursors in humans.

Journal article Science · July 31, 2025 A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-ta ... Full text Link to item Cite

Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.

Journal article Science · July 31, 2025 A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phas ... Full text Link to item Cite

Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial.

Journal article Sci Transl Med · July 30, 2025 mRNA technology might accelerate development of an urgently needed preventive human immunodeficiency virus (HIV) vaccine. We evaluated the safety and immunogenicity of three mRNA-encoded envelope trimers, including two doses of soluble and membrane-anchore ... Full text Link to item Cite

Optimizing human B cell repertoire analyses to interpret clinical data and design sequential HIV vaccines.

Journal article NPJ Vaccines · July 17, 2025 Advances in HIV vaccine development focus on eliciting broadly neutralizing antibodies (bNAbs) through next-generation immunogens. Human trials are testing these candidates for their ability to initiate B cell maturation. This workshop report reviews emerg ... Full text Link to item Cite

Prior human endemic coronavirus exposure does not affect humoral responses to SARS-CoV-2 protein vaccines.

Journal article NPJ Vaccines · July 13, 2025 We included measurement of pre-existing immunity to human endemic coronaviruses (HCoV) in a Phase I/II study of SARS-CoV-2 spike protein vaccine candidates. A Binding Antibody Multiplex Assay measured HCoV-specific IgG to the receptor binding domain or ful ... Full text Link to item Cite

Fixed dosing versus weight-based dosing of HIV-1 prophylactic monoclonal antibodies in adults: a post-hoc, cross-protocol pharmacokinetics modelling study.

Journal article EBioMedicine · July 2025 BACKGROUND: Pharmacokinetic (PK) modelling and simulations have been used to support label changes of dosing levels or strategies for multiple marketed therapeutic monoclonal antibodies (mAbs). Using data from early-phase clinical trials in adults without ... Full text Link to item Cite

Safety and implementation of phase I randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns.

Journal article J Clin Invest · June 2, 2025 BACKGROUNDThe neonatal immune system is uniquely poised to generate broadly neutralizing antibodies (bnAbs), and thus infants are ideal for evaluating HIV vaccine candidates. We present the design and safety of a new-in-infants glucopyranosyl lipid A-stabl ... Full text Link to item Cite

Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, a V2 specific HIV-1 broadly neutralising antibody, infused intravenously or subcutaneously in people without HIV-1 in the USA (HVTN 140/HPTN 101 part A): a first-in-human, phase 1 randomised trial.

Journal article Lancet HIV · June 2025 BACKGROUND: PGDM1400LS is a human monoclonal antibody targeting the HIV envelope V2 apex with a lysine-serine modification intended to enhance serum and tissue half-lives and is being considered for use in combination monoclonal antibody trials. We sought ... Full text Link to item Cite

Engineering Sustained-Release Broadly Neutralizing Antibody Formulations.

Journal article bioRxiv · June 1, 2025 Sustained serum levels of broadly neutralizing antibodies (bnAbs) are crucial for effective passive immunization against infectious diseases as protection persists only while these bnAbs remain at adequate concentrations within the body. Current obstacles, ... Full text Link to item Cite

Distinct immune responses in people living with HIV following SARS-CoV-2 recovery.

Journal article Commun Med (Lond) · April 23, 2025 BACKGROUND: SARS-CoV-2 infection results in greater disease severity among immunocompromised individuals compared to healthy individuals. However, there is conflicting information about the impact of chronic HIV infection on immune responses to SARS-CoV-2 ... Full text Link to item Cite

A global collaboration for systematic analysis of broad-ranging antibodies against the SARS-CoV-2 spike protein.

Journal article Cell Rep · April 22, 2025 The Coronavirus Immunotherapeutic Consortium (CoVIC) conducted side-by-side comparisons of over 400 anti-SARS-CoV-2 spike therapeutic antibody candidates contributed by large and small companies as well as academic groups on multiple continents. Nine refer ... Full text Link to item Cite

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

Journal article J Infect Dis · April 15, 2025 Utilizing transiently transfected cell lines could significantly reduce manufacturing timelines for protein subunit vaccines. This trial compared safety and immunogenicity of human immunodeficiency virus (HIV) envelope CH505TF gp120 vaccines produced by up ... Full text Link to item Cite

Computationally Selected Multivalent HIV-1 Subtype C Vaccine Protects Against Heterologous SHIV Challenge.

Journal article Vaccines (Basel) · February 24, 2025 Background: The RV144 trial in Thailand is the only HIV-1 vaccine efficacy trial to date to demonstrate any efficacy. Genetic signatures suggested that antibodies targeting the variable loop 2 (V2) of the HIV-1 envelope played an important protective role. ... Full text Link to item Cite

Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV.

Journal article BMC Immunol · February 19, 2025 VRC07-523LS is a safe and well-tolerated monoclonal antibody (mAb) targeting the CD4 binding site on the HIV envelope (Env) trimer. Efficacy of VRC07-523LS, in combination with mAbs targeting other HIV epitopes, will be evaluated in upcoming trials to prev ... Full text Link to item Cite

A Pentavalent HIV-1 Subtype C Vaccine Containing Computationally Selected gp120 Strains Improves the Breadth of V1V2 Region Responses.

Journal article Vaccines (Basel) · January 28, 2025 BACKGROUND: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV- ... Full text Link to item Cite

Effect of timing of casirivimab and imdevimab administration relative to mRNA-1273 COVID-19 vaccination on vaccine-induced SARS-CoV-2 neutralising antibody responses: a prospective, open-label, phase 2, randomised controlled trial.

Journal article Lancet Infect Dis · January 2025 BACKGROUND: Deeper insight is needed on how monoclonal antibodies (mAbs) affect vaccine-mediated immune responses when targeting the same protein. We describe the first prospective randomised trial designed to understand mAb-mediated alterations in vaccine ... Full text Link to item Cite

Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial.

Journal article Lancet HIV · January 2025 BACKGROUND: Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.LS and VRC07-523LS mAbs for safety and pharmacokinetics in adults. METHODS: In this first-in-hu ... Full text Link to item Cite

ALVAC-prime and monomeric gp120 protein boost induces distinct HIV-1 specific humoral and cellular responses compared with adenovirus-prime and trimeric gp140 protein boost.

Journal article PLOS Glob Public Health · 2025 Although clade-specific and cross-clade mosaic prime-boost HIV-1 vaccine regimens were advanced to the HVTN 702 and HVTN 705 efficacy trials, neither regimen prevented HIV acquisition. The respective Phase 1/2a studies, HVTN 100 (NCT02404311) and HVTN 117/ ... Full text Link to item Cite

Retrospective analysis of sex-disaggregated immune responses to ALVAC-HIV and bivalent subtype C gp120/MF59 HIV vaccines.

Journal article Front Immunol · 2025 INTRODUCTION: Generally, individuals assigned female at birth (AFAB) develop greater immunogenicity to various vaccines than individuals assigned male at birth (AMAB). Little is known about sex-disaggregated immunogenicity to HIV-1 vaccines. We disaggregat ... Full text Link to item Cite

Myeloid cell recruitment and activation through systemic and mucosae-directed cytokine therapy.

Journal article Immunol Cell Biol · 2025 Myeloid cells play critical roles as Fc effector cells in antibody-mediated immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that promotes the recruitment and activation of multiple myeloid populations and has b ... Full text Link to item Cite

Immunogenicity and protection mediated by dmLT and alum adjuvants for an HIV-1 vaccine.

Journal article Front Immunol · 2025 The development of an effective HIV-1 vaccine is of paramount importance to global health. Here, we compared the influence of two adjuvants, Escherichia coli double-mutant heat-labile toxin (dmLT) and alum, on the protective immunity induced by a cyclicall ... Full text Link to item Cite

Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial.

Journal article Lancet Infect Dis · November 2024 BACKGROUND: HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure pr ... Full text Link to item Cite

GeM-LR: Discovering predictive biomarkers for small datasets in vaccine studies.

Journal article PLoS Comput Biol · November 2024 Despite significant progress in vaccine research, the level of protection provided by vaccination can vary significantly across individuals. As a result, understanding immunologic variation across individuals in response to vaccination is important for dev ... Full text Link to item Cite

Safety and immunogenicity of CD40.HIVRI.Env, a dendritic cell-based HIV vaccine, in healthy HIV-uninfected adults: a first-in-human randomized, placebo-controlled, dose-escalation study (ANRS VRI06).

Journal article EClinicalMedicine · November 2024 BACKGROUND: Current HIV prophylactic vaccines evaluate HIV Env as purified proteins. CD40.HIVRI.Env is an innovative antigen delivery targeting gp140 Env from HIV Clade C 96ZM651 to CD40-expressing antigen-presenting cells, thus harnessing the intrinsic im ... Full text Link to item Cite

Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response.

Journal article Nat Commun · October 22, 2024 Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILC ... Full text Link to item Cite

Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns.

Journal article medRxiv · October 17, 2024 BACKGROUND: The neonatal immune system is uniquely poised to generate broadly neutralizing antibodies (bnAbs) and thus infants are ideal for evaluating HIV vaccine candidates. We present the design and safety of a novel glucopyranosyl lipid A (GLA)-stable ... Full text Link to item Cite

Identification of RTS,S/AS01 vaccine-induced humoral biomarkers predictive of protection against controlled human malaria infection.

Journal article JCI Insight · October 8, 2024 BACKGROUNDThe mechanism(s) responsible for the efficacy of WHO-recommended malaria vaccine RTS,S/AS01 are not completely understood. We previously identified RTS,S vaccine-induced Plasmodium falciparum circumsporozoite protein-specific (PfCSP-specific) ant ... Full text Link to item Cite

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

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

The Climate Change Burden on Immune Health: Are Persons Living with HIV More at Risk?

Journal article AIDS Res Hum Retroviruses · October 2024 Climate change poses one of the most significant modern threats to overall human health,especially for vulnerable populations including persons living with HIV (PLWH). In this perspective, we specifically explore the concept of immune resilience in human h ... Full text Link to item Cite

Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study.

Journal article EBioMedicine · October 2024 BACKGROUND: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and ... Full text Open Access Link to item Cite

Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model.

Journal article Immunohorizons · September 1, 2024 Cutaneous mycobacterial infections cause substantial morbidity and are challenging to diagnose and treat. An improved understanding of the dermal immune response to mycobacteria may inspire new therapeutic approaches. We conducted a controlled human infect ... Full text Link to item Cite

Non-HIV Vaccine-Induced Immune Responses as Potential Baseline Immunogenicity Predictors of ALVAC-HIV and AIDSVAX B/E-Induced Immune Responses.

Journal article Viruses · August 27, 2024 Identifying correlations between immune responses elicited via HIV and non-HIV vaccines could aid the search for correlates of HIV protection and increase statistical power in HIV vaccine-efficacy trial designs. An exploratory objective of the HVTN 097 pha ... Full text Link to item Cite

Protein Dose-Sparing Effect of AS01B Adjuvant in a Randomized Preventive HIV Vaccine Trial of ALVAC-HIV (vCP2438) and Adjuvanted Bivalent Subtype C gp120.

Journal article J Infect Dis · August 16, 2024 BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env ... Full text Link to item Cite

Safety and Immunogenicity of a DNA Vaccine With Subtype C gp120 Protein Adjuvanted With MF59 or AS01B: A Phase 1/2a HIV-1 Vaccine Trial.

Journal article J Acquir Immune Defic Syndr · August 1, 2024 BACKGROUND: An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, a ... Full text Link to item Cite

Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119.

Journal article JCI Insight · August 1, 2024 BACKGROUNDAn HIV-1 DNA vaccine composed of 7 highly conserved, structurally important elements (conserved elements, CE) of p24Gag was tested in a phase I randomized, double-blind clinical trial (HVTN 119, NCT03181789) in people without HIV. DNA vaccination ... Full text Link to item Cite

A comparative immunological assessment of multiple clinical-stage adjuvants for the R21 malaria vaccine in nonhuman primates.

Journal article Sci Transl Med · July 31, 2024 Authorization of the Matrix-M (MM)-adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization for malaria prevention in children are a milestone in the fight against malaria. Yet, our understanding of the inna ... Full text Link to item Cite

Is HIV epidemic control by 2030 realistic?

Journal article Lancet HIV · July 2024 Rates of new HIV acquisition remain unacceptably high in most populations in low-income, middle-income, and high-income settings despite advances in treatment and prevention strategies. Although biomedical advances in primary prevention of new infections e ... Full text Link to item Cite

The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy.

Journal article AIDS · June 1, 2024 OBJECTIVE: The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART). DESIGN: AIDS Clinical Trials Group A5369 w ... Full text Link to item Cite

Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions.

Journal article PLoS Pathog · June 2024 Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizin ... Full text Link to item Cite

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

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

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

HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces human autologous tier-2 neutralizing antibodies.

Journal article medRxiv · May 9, 2024 UNLABELLED: Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140, formulated with a nov ... Full text Link to item Cite

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

Journal article Lancet HIV · May 2024 BACKGROUND: An effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA-protein HIV ... Full text Link to item Cite

Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV.

Journal article Pharmaceutics · April 27, 2024 Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing bindi ... Full text Link to item Cite

Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial.

Journal article PLoS Med · March 2024 BACKGROUND: Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen mod ... Full text Link to item Cite

Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques.

Journal article Elife · February 22, 2024 CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and fu ... Full text Link to item Cite

Polytopic fractional delivery of an HIV vaccine alters cellular responses and results in increased epitope breadth in a phase 1 randomized trial.

Journal article EBioMedicine · February 2024 BACKGROUND: Elicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection sites ... Full text Link to item Cite

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

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

A candidate antibody drug for prevention of malaria.

Journal article Nat Med · January 2024 Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategi ... Full text Link to item Cite

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

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

Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity.

Journal article Pathog Immun · 2024 BACKGROUND: Antibody-dependent cell-mediated cytotoxic (ADCC) response mediated by natural killer (NK) cells correlates with decreased infection risk in studies involving simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV), and h ... Full text Link to item Cite

Cryptic-site-specific antibodies to the SARS-CoV-2 receptor binding domain can retain functional binding affinity to spike variants.

Journal article J Virol · December 21, 2023 Multiple SARS-CoV-2 variants of concern have emerged and caused a significant number of infections and deaths worldwide. These variants of concern contain mutations that might significantly affect antigen-targeting by antibodies. It is therefore important ... Full text Link to item Cite

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

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

Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein.

Journal article Cell Rep · November 28, 2023 IGHV3-33-encoded antibodies are prevalent in the human humoral response against the Plasmodium falciparum circumsporozoite protein (PfCSP). Among VH3-33 antibodies, cross-reactivity between PfCSP major repeat (NANP), minor (NVDP), and junctional (NPDP) mot ... Full text Link to item Cite

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

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

Parameter estimation and identifiability analysis for a bivalent analyte model of monoclonal antibody-antigen binding.

Journal article Anal Biochem · October 15, 2023 Surface plasmon resonance (SPR) is an extensively used technique to characterize antigen-antibody interactions. Affinity measurements by SPR typically involve testing the binding of antigen in solution to monoclonal antibodies (mAbs) immobilized on a chip ... Full text Link to item Cite

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

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

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

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

Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions.

Journal article bioRxiv · July 26, 2023 Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizin ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

Coronavirus Immunotherapeutic Consortium Database.

Journal article Database (Oxford) · February 10, 2023 The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seen multiple anti-SARS-CoV-2 antibodies being generated globally. It is difficult, however, to assemble a useful compendium of ... Full text Link to item Cite

Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

Journal article Cell Rep · January 31, 2023 The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronav ... Full text Link to item Cite

A tool for evaluating heterogeneity in avidity of polyclonal antibodies.

Journal article Front Immunol · 2023 Diversity in specificity of polyclonal antibody (pAb) responses is extensively investigated in vaccine efficacy or immunological evaluations, but the heterogeneity in antibody avidity is rarely probed as convenient tools are lacking. Here we have developed ... Full text Link to item Cite

H3N2 influenza hemagglutination inhibition method qualification with data driven statistical methods for human clinical trials.

Journal article Front Immunol · 2023 INTRODUCTION: Hemagglutination inhibition (HAI) antibody titers to seasonal influenza strains are important surrogates for vaccine-elicited protection. However, HAI assays can be variable across labs, with low sensitivity across diverse viruses due to lack ... Full text Open Access Link to item Cite

Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques.

Journal article Front Immunol · 2023 INTRODUCTION: An efficacious HIV vaccine will need to elicit a complex package of innate, humoral, and cellular immune responses. This complex package of responses to vaccine candidates has been studied and yielded important results, yet it has been a recu ... Full text Link to item Cite

Cross-protocol assessment of induction and durability of VISP/R in HIV preventive vaccine trial participants.

Journal article PLOS Glob Public Health · 2023 Candidate HIV vaccines are designed to induce antibodies to various components of the HIV virus. An unintended result of these antibodies is that they may also be detected by commercial HIV diagnostic kits designed to detect an immune response to HIV acqui ... Full text Link to item Cite

TitrationAnalysis: a tool for high throughput binding kinetics data analysis for multiple label-free platforms.

Journal article Gates Open Res · 2023 Label-free techniques including Surface Plasmon Resonance (SPR) and Biolayer Interferometry (BLI) are biophysical tools widely used to collect binding kinetics data of bimolecular interactions. To efficiently analyze SPR and BLI binding kinetics data, we h ... Full text Link to item Cite

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques.

Journal article Front Immunol · 2023 Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs re ... Full text Open Access Link to item Cite

Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing.

Journal article Front Immunol · 2023 Fcγ receptors (FcγRs) are membrane-bound glycoproteins that bind to the fragment crystallizable (Fc) constant regions of IgG antibodies. Interactions between IgG immune complexes and FcγRs can initiate signal transduction that mediates important components ... Full text Link to item Cite

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

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

Vaccination induces HIV broadly neutralizing antibody precursors in humans.

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

Lower SARS-CoV-2-specific humoral immunity in people living with HIV-1 recovered from nonhospitalized COVID-19.

Journal article JCI Insight · November 8, 2022 People living with HIV-1 (PLWH) exhibit more rapid antibody decline following routine immunization and elevated baseline chronic inflammation than people without HIV-1 (PWOH), indicating potential for diminished humoral immunity during SARS-CoV-2 infection ... Full text Link to item Cite

High-density binding to Plasmodium falciparum circumsporozoite protein repeats by inhibitory antibody elicited in mouse with human immunoglobulin repertoire.

Journal article PLoS Pathog · November 2022 Antibodies targeting the human malaria parasite Plasmodium falciparum circumsporozoite protein (PfCSP) can prevent infection and disease. PfCSP contains multiple central repeating NANP motifs; some of the most potent anti-infective antibodies against malar ... Full text Link to item Cite

Safety and Pharmacokinetics of Intravenous 10-1074 and VRC01LS in Young Children.

Journal article J Acquir Immune Defic Syndr · October 1, 2022 BACKGROUND: Broadly neutralizing monoclonal antibodies (bNAbs) suppress HIV-1 RNA and may deplete residual viral reservoirs. We evaluated the safety and pharmacokinetics (PK) of dual intravenous VRC01LS and 10-1074 in very early-treated children with HIV-1 ... Full text Link to item Cite

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

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

Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk.

Journal article J Infect Dis · August 24, 2022 BACKGROUND: The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition ri ... Full text Link to item Cite

Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans.

Journal article NPJ Vaccines · August 4, 2022 Adjuvants can alter the magnitude, characteristics, and persistence of the humoral response to protein vaccination. HIV vaccination might benefit from tailored adjuvant choice as raising a durable and protective response to vaccination has been exceptional ... Full text Link to item Cite

A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques.

Journal article Sci Immunol · July 22, 2022 The rising global HIV-1 burden urgently requires vaccines capable of providing heterologous protection. Here, we developed a clade C HIV-1 vaccine consisting of priming with modified vaccinia Ankara (MVA) and boosting with cyclically permuted trimeric gp12 ... Full text Link to item Cite

The quest for vaccine-induced immune correlates of protection against tuberculosis.

Journal article Vaccine Insights · July 2022 Immunization strategies against tuberculosis (TB) that confer better protection than neonatal vaccination with the 101-year-old Bacille Calmette-Guerin (BCG) are urgently needed to control the epidemic, but clinical development is hampered by a lack of est ... Full text Link to item Cite

Development of flow cytometry-based assays to assess the ability of antibodies to bind to SARS-CoV-2-infected and spike-transfected cells and mediate NK cell degranulation.

Journal article Cytometry A · June 2022 Since the beginning of the SARS-CoV-2 pandemic, antibody responses and antibody effector functions targeting SARS-CoV-2-infected cells have been understudied. Consequently, the role of these types of antibodies in SARS-CoV-2 disease (COVID-19) and immunity ... Full text Link to item Cite

Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial.

Journal article Nat Med · June 2022 HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb therapy may be needed for robust suppression of viremia. We performed a two-part study consisting of a single-center, r ... Full text Link to item Cite

A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.

Journal article PLoS Pathog · May 2022 Transmitted/founder (T/F) HIV-1 envelope proteins (Envs) from infected individuals that developed neutralization breadth are likely to possess inherent features desirable for vaccine immunogen design. To explore this premise, we conducted an immunization s ... Full text Link to item Cite

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

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

Broadly binding and functional antibodies and persisting memory B cells elicited by HIV vaccine PDPHV.

Journal article NPJ Vaccines · February 9, 2022 Since publishing our original reports on the safety and immunogenicity of a polyvalent DNA prime-protein boost HIV vaccine (PDPHV) which elicited high titer antibody responses with broad specificity, neutralizing activities to multiple HIV-1 subtypes, as w ... Full text Link to item Cite

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

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

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

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

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

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

Multi-trial analysis of HIV-1 envelope gp41-reactive antibodies among global recipients of candidate HIV-1 vaccines.

Journal article Front Immunol · 2022 Many participants in HIV-1 vaccine trials, who have not previously been exposed to or vaccinated against HIV-1, display serum immunoglobulin antibodies that bind the gp41 region of HIV-1 envelope prior to vaccination. Previous studies have hypothesized tha ... Full text Link to item Cite

Salmonella Typhi Vi capsule prime-boost vaccination induces convergent and functional antibody responses.

Journal article Sci Immunol · October 29, 2021 Vaccine development to prevent Salmonella Typhi infections has accelerated over the past decade, resulting in licensure of new vaccines, which use the Vi polysaccharide (Vi PS) of the bacterium conjugated to an unrelated carrier protein as the active compo ... Full text Open Access Link to item Cite

Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.

Journal article Science · October 22, 2021 Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated ... Full text Link to item Cite

The transcription factor CREB1 is a mechanistic driver of immunogenicity and reduced HIV-1 acquisition following ALVAC vaccination.

Journal article Nat Immunol · October 2021 Development of effective human immunodeficiency virus 1 (HIV-1) vaccines requires synergy between innate and adaptive immune cells. Here we show that induction of the transcription factor CREB1 and its target genes by the recombinant canarypox vector ALVAC ... Full text Link to item Cite

Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial.

Journal article Nat Med · October 2021 Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial ... Full text Link to item Cite

Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as a potential mechanism of vaccine-induced protection against HIV-1.

Journal article Elife · September 17, 2021 A gene signature was previously found to be correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus and simian-human immunodeficiency virus challenge models in non-human primates. In this report, we investigated the presenc ... Full text Link to item Cite

Four-parameter paired response curve for serial dilution assays.

Journal article J Biopharm Stat · September 3, 2021 Newer immunoassay platforms offer improved signal-to-noise ratio but are more expensive. Thus, it is more cost efficient to perform these assays at a few selected, rather than a full series of, sample dilutions. We propose a new four-parameter paired respo ... Full text Link to item Cite

Mind the gap from research laboratory to clinic: Challenges and opportunities for next-generation assays in human diseases.

Journal article Vaccine · August 31, 2021 Modern vaccinology has experienced major conceptual and technological advances over the past 30 years. These include atomic-level structures driving immunogen design, new vaccine delivery methods, powerful adjuvants, and novel animal models. In addition, u ... Full text Link to item Cite

Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection.

Journal article NPJ Vaccines · August 30, 2021 RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify c ... Full text Link to item Cite

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge.

Journal article J Clin Invest · August 16, 2021 BackgroundVRC01, a potent, broadly neutralizing monoclonal antibody, inhibits simian-HIV infection in animal models. The HVTN 104 study assessed the safety and pharmacokinetics of VRC01 in humans. We extend the clinical evaluation to determine intravenousl ... Full text Link to item Cite

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

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

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

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

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

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

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

Meta-analysis of HIV-1 vaccine elicited mucosal antibodies in humans.

Journal article NPJ Vaccines · April 15, 2021 We studied mucosal immune responses in six HIV-1 vaccine trials investigating different envelope (Env)-containing immunogens. Regimens were classified into four categories: DNA/vector, DNA/vector plus protein, protein alone, and vector alone. We measured H ... Full text Link to item Cite

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

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

In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP).

Journal article Sci Rep · March 5, 2021 Plasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a ... Full text Open Access Link to item Cite

Innate immune signatures to a partially-efficacious HIV vaccine predict correlates of HIV-1 infection risk.

Journal article PLoS Pathog · March 2021 The pox-protein regimen tested in the RV144 trial is the only vaccine strategy demonstrated to prevent HIV-1 infection. Subsequent analyses identified antibody and cellular immune responses as correlates of risk (CoRs) for HIV infection. Early predictors o ... 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

Vi-specific serological correlates of protection for typhoid fever.

Journal article J Exp Med · February 1, 2021 Typhoid Vi vaccines have been shown to be efficacious in children living in endemic regions; however, a widely accepted correlate of protection remains to be established. We applied a systems serology approach to identify Vi-specific serological correlates ... Full text Link to item Cite

Magnitude, Specificity, and Avidity of Sporozoite-Specific Antibodies Associate with Protection Status and Distinguish among RTS,S/AS01 Dose Regimens

Journal article Open Forum Infectious Diseases · February 1, 2021 Background: The malaria vaccine, RTS,S/AS01, demonstrated an enhanced efficacy (86.7%) in a delayed third fractional dose (0.1.7Fx) regimen in controlled human malaria infection trials compared with a standard full-dose (0.1.2) regimen (62.5%). To understa ... Full text Cite

Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein.

Journal article Clin Infect Dis · January 23, 2021 BACKGROUND: The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immuno ... Full text Link to item Cite

Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses.

Journal article J Virol · January 13, 2021 Daily burden and clinical toxicities associated with antiretroviral therapy (ART) emphasize the need for alternative strategies to induce long-term human immunodeficiency virus (HIV) remission upon ART cessation. Broadly neutralizing antibodies (bNAbs) can ... Full text Link to item Cite

SIMON: Open-Source Knowledge Discovery Platform.

Journal article Patterns (N Y) · January 8, 2021 Data analysis and knowledge discovery has become more and more important in biology and medicine with the increasing complexity of biological datasets, but the necessarily sophisticated programming skills and in-depth understanding of algorithms needed pos ... Full text Link to item Cite

Functional Homology for Antibody-Dependent Phagocytosis Across Humans and Rhesus Macaques.

Journal article Front Immunol · 2021 Analyses of human clinical HIV-1 vaccine trials and preclinical vaccine studies performed in rhesus macaque (RM) models have identified associations between non-neutralizing Fc Receptor (FcR)-dependent antibody effector functions and reduced risk of infect ... Full text Link to item Cite

Comprehensive Data Integration Approach to Assess Immune Responses and Correlates of RTS,S/AS01-Mediated Protection From Malaria Infection in Controlled Human Malaria Infection Trials.

Journal article Front Big Data · 2021 RTS,S/AS01 (GSK) is the world's first malaria vaccine. However, despite initial efficacy of almost 70% over the first 6 months of follow-up, efficacy waned over time. A deeper understanding of the immune features that contribute to RTS,S/AS01-mediated prot ... Full text Link to item Cite

Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS.

Journal article Front Immunol · 2021 The outcome of the recent Antibody Mediated Prevention (AMP) trials that tested infusion of the broadly neutralizing antibody (bnAb) VRC01 provides proof of concept for blocking infection from sensitive HIV-1 strains. These results also open up the possibi ... Full text Link to item Cite

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

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

Structure and Fc-Effector Function of Rhesusized Variants of Human Anti-HIV-1 IgG1s.

Journal article Front Immunol · 2021 Passive transfer of monoclonal antibodies (mAbs) of human origin into Non-Human Primates (NHPs), especially those which function predominantly by a Fc-effector mechanism, requires an a priori preparation step, in which the human mAb is reengineered to an e ... Full text Link to item Cite

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

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

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

Journal article Lancet HIV · October 2020 BACKGROUND: Bioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared the safety, tolerability, and immunogenicity of a newly developed, tetravalent Ad26 vaccine with the previously tested trivale ... Full text Link to item Cite

Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.

Journal article PLoS Pathog · September 2020 To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal m ... Full text Link to item Cite

RhCMV serostatus and vaccine adjuvant impact immunogenicity of RhCMV/SIV vaccines.

Journal article Sci Rep · August 20, 2020 Rhesus cytomegalovirus (RhCMV) strain 68-1-vectored simian immunodeficiency virus (RhCMV/SIV) vaccines are associated with complete clearance of pathogenic SIV challenge virus, non-canonical major histocompatibility complex restriction, and absent antibody ... Full text Link to item Cite

Impact of vaccine type on HIV-1 vaccine elicited antibody durability and B cell gene signature.

Journal article Sci Rep · August 3, 2020 Efficacious HIV-1 vaccination requires elicitation of long-lived antibody responses. However, our understanding of how different vaccine types elicit durable antibody responses is lacking. To assess the impact of vaccine type on antibody responses, we meas ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa.

Journal article EClinicalMedicine · April 2020 BACKGROUND: Tuberculosis (TB) remains the leading cause of infectious disease-related death. Recently, a trial of BCG revaccination and vaccination with H4:IC31, a recombinant protein vaccine, in South African adolescents (Aeras C-040-404) showed efficacy ... 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

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

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

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

A MUC16 IgG Binding Activity Selects for a Restricted Subset of IgG Enriched for Certain Simian Immunodeficiency Virus Epitope Specificities.

Journal article J Virol · February 14, 2020 We have recently shown that MUC16, a component of the glycocalyx of some mucosal barriers, has elevated binding to the G0 glycoform of the Fc portion of IgG. Therefore, IgG from patients chronically infected with human immunodeficiency virus (HIV), who typ ... Full text Link to item Cite

Persistence of vaccine-elicited immune response up to 14 years post-HIV gp120-NefTat/AS01B vaccination.

Journal article Vaccine · February 11, 2020 BACKGROUND: Vaccines eliciting protective and persistent immune responses against multiple human immunodeficiency virus type 1 (HIV-1) clades are needed. This study evaluated the persistence of immune responses induced by an investigational, AS01-adjuvante ... Full text Link to item Cite

HIV-1 Vaccine Sequences Impact V1V2 Antibody Responses: A Comparison of Two Poxvirus Prime gp120 Boost Vaccine Regimens.

Journal article Sci Rep · February 7, 2020 In the RV144 trial, vaccine-induced V1V2 IgG correlated with decreased HIV-1 risk. We investigated circulating antibody specificities in two phase 1 poxvirus prime-protein boost clinical trials conducted in South Africa: HVTN 097 (subtype B/E) and HVTN 100 ... Full text Link to item Cite

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

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

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

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

Hinge length contributes to the phagocytic activity of HIV-specific IgG1 and IgG3 antibodies.

Journal article PLoS Pathog · February 2020 Antibody functions such as neutralization require recognition of antigen by the Fab region, while effector functions are additionally mediated by interactions of the Fc region with soluble factors and cellular receptors. The efficacy of individual antibodi ... Full text Link to item Cite

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

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

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

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

Methods for comparing durability of immune responses between vaccine regimens in early-phase trials.

Journal article Stat Methods Med Res · January 2020 The ability to produce a long-lasting, or durable, immune response is a crucial characteristic of many highly effective vaccines. A goal of early-phase vaccine trials is often to compare the immune response durability of multiple tested vaccine regimens. O ... Full text Link to item Cite

Framework Mutations of the 10-1074 bnAb Increase Conformational Stability, Manufacturability, and Stability While Preserving Full Neutralization Activity.

Journal article J Pharm Sci · January 2020 The broadly neutralizing anti-HIV antibody, 10-1074, is a highly somatically hypermutated IgG1 being developed for prophylaxis in sub-Saharan Africa. A series of algorithms were applied to identify potentially destabilizing residues in the framework of the ... Full text Link to item Cite

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

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

Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans.

Journal article PLoS One · 2020 BACKGROUND: HIV vaccine trials routinely measure multiple vaccine-elicited immune responses to compare regimens and study their potential associations with protection. Here we employ unsupervised learning tools facilitated by a bidirectional power transfor ... Full text Link to item 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

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

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

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

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

Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial.

Journal article J Virol · November 1, 2019 HIV Vaccine Trials Network (HVTN) 505 was a phase 2b efficacy trial of a DNA/recombinant adenovirus 5 (rAd5) HIV vaccine regimen. Although the trial was stopped early for lack of overall efficacy, later correlates of risk and sieve analyses generated the h ... Full text Link to item Cite

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

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

Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk.

Journal article J Clin Invest · November 1, 2019 HVTN 505 is a preventative vaccine efficacy trial testing DNA followed by recombinant adenovirus serotype 5 (rAd5) in circumcised, Ad5-seronegative men and transgendered persons who have sex with men in the United States. Identified immune correlates of lo ... Full text Link to item Cite

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

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

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

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

Repeated semen exposure decreases cervicovaginal SIVmac251 infection in rhesus macaques.

Journal article Nat Commun · August 21, 2019 Semen is the vehicle for virion dissemination in the female reproductive tract (FRT) in male-to-female HIV transmission. Recent data suggests that higher frequency semen exposure is associated with activation of anti-HIV mechanisms in HIV negative sex work ... Full text Link to item Cite

HLA class II-Restricted CD8+ T cells in HIV-1 Virus Controllers.

Journal article Sci Rep · July 15, 2019 A paradigm shifting study demonstrated that induction of MHC class E and II-restricted CD8+ T cells was associated with the clearance of SIV infection in rhesus macaques. Another recent study highlighted the presence of HIV-1-specific class II-restricted C ... Full text Open Access Link to item Cite

HIV Research for Prevention 2018: From Research to Impact Conference Summary and Highlights.

Journal article AIDS Res Hum Retroviruses · July 2019 The HIV Research for Prevention (HIVR4P) conference is dedicated to advancing HIV prevention research, responding to a growing consensus that effective and durable prevention will require a combination of approaches as well as unprecedented collaboration a ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response.

Journal article J Clin Invest · March 1, 2019 It is widely believed that protection against acquisition of HIV or SIV infection requires anti-envelope (anti-Env) antibodies, and that cellular immunity may affect viral loads but not acquisition, except in special cases. Here we provide evidence to the ... Full text Link to item Cite

Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.

Journal article Nat Commun · February 20, 2019 The RV144 vaccine trial showed reduced risk of HIV-1 acquisition by 31.2%, although mechanisms that led to protection remain poorly understood. Here we identify transcriptional correlates for reduced HIV-1 acquisition after vaccination. We assess the trans ... 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

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

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

HIV-1/SIV humoral responses in external secretions

Journal article Current Immunology Reviews · January 1, 2019 The protective function of mucosal HIV-1- or SIV-specific antibodies against viral infection has stimulated extensive studies of their Ig isotype association with differences in specificity and in effector functions. In contrast to many mucosally acquired ... Full text Cite

Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study.

Journal article PLoS One · 2019 BACKGROUND: Additional forms of pre-exposure prophylaxis are needed to prevent HIV-1 infection. 3BNC117 and 10-1074 are broadly neutralizing anti-HIV-1 antibodies that target non-overlapping epitopes on the HIV-1 envelope. We investigated the safety, toler ... Full text Link to item Cite

IgA and IgG1 Specific to Vi Polysaccharide of Salmonella Typhi Correlate With Protection Status in a Typhoid Fever Controlled Human Infection Model.

Journal article Front Immunol · 2019 Vaccination against Salmonella Typhi using the Vi capsular polysaccharide, a T-cell independent antigen, can protect from the development of typhoid fever. This implies that antibodies to Vi alone can protect in the absence of a T cell-mediated immune resp ... Full text Link to item Cite

Vaccine-Induced Antibodies Mediate Higher Antibody-Dependent Cellular Cytotoxicity After Interleukin-15 Pretreatment of Natural Killer Effector Cells.

Journal article Frontiers in immunology · January 2019 The secondary analyses for correlates of risk of infection in the RV144 HIV-1 vaccine trial implicated vaccine-induced antibody-dependent cellular cytotoxicity (ADCC) responses in the observed protection, highlighting the importance of assessing such respo ... Full text Open Access Cite

Human gut microbiota is associated with HIV-reactive immunoglobulin at baseline and following HIV vaccination.

Journal article PLoS One · 2019 Antibodies that recognize commensal microbial antigens may be cross reactive with a part of the human immunodeficiency virus (HIV) envelope glycoprotein gp41. To improve understanding of the role of the microbiota in modulating the immune response to HIV v ... Full text Link to item Cite

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

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

Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals.

Journal article Nat Med · November 2018 Monotherapy of HIV-1 infection with single antiretroviral agents is ineffective because error-prone HIV-1 replication leads to the production of drug-resistant viral variants1,2. Combinations of drugs can establish long-term control, however, antiretrovira ... Full text Link to item Cite

RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses.

Journal article Cell · October 4, 2018 HIV-1 broadly neutralizing antibodies (bnAbs) are difficult to induce with vaccines but are generated in ∼50% of HIV-1-infected individuals. Understanding the molecular mechanisms of host control of bnAb induction is critical to vaccine design. Here, we pe ... Full text Link to item Cite

Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV.

Journal article Nat Med · October 2018 Antibodies are the primary correlate of protection for most licensed vaccines; however, their mechanisms of protection may vary, ranging from physical blockade to clearance via the recruitment of innate immunity. Here, we uncover striking functional divers ... Full text Link to item Cite

Combination therapy with anti-HIV-1 antibodies maintains viral suppression.

Journal article Nature · September 2018 Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal ant ... Full text Link to item Cite

Qualified Biolayer Interferometry Avidity Measurements Distinguish the Heterogeneity of Antibody Interactions with Plasmodium falciparum Circumsporozoite Protein Antigens.

Journal article J Immunol · August 15, 2018 Ab avidity is a measure of the overall strength of Ab-Ag interactions and hence is important for understanding the functional efficiency of Abs. In vaccine evaluations, Ab avidity measurements can provide insights into immune correlates of protection and g ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Application of area scaling analysis to identify natural killer cell and monocyte involvement in the GranToxiLux antibody dependent cell-mediated cytotoxicity assay.

Journal article Cytometry A · April 2018 Several different assay methodologies have been described for the evaluation of HIV or SIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC). Commonly used assays measure ADCC by evaluating effector cell functions, or by detecting elimination o ... Full text Open Access Link to item Cite

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

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

Erratum: Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs (Blood Advances (2017) 1:25 (2329-2342) DOI: 10.1182/bloodadvances.2017011411)

Journal article Blood Advances · March 13, 2018 On page 2339, under "Authorship," the contribution paragraph should have read, "J.R.F., D.E.Z., G.A., and R.A.S. conceived the study and wrote the paper; E.S., N.M.V., P.M., E.D.G., S.W.B., P.S., M.S., S.J., A.S., and D.T.O. developed the vaccine formulati ... Full text Cite

Predominant envelope variable loop 2-specific and gp120-specific antibody-dependent cellular cytotoxicity antibody responses in acutely SIV-infected African green monkeys.

Journal article Retrovirology · March 9, 2018 BACKGROUND: The initial envelope (Env)-specific antibody response in acutely HIV-1-infected individuals and simian immunodeficiency virus (SIV)-infected rhesus monkeys (RMs) is dominated by non-neutralizing antibodies targeting Env gp41. In contrast, natur ... 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

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine.

Journal article J Virol · January 1, 2018 In the RV144 vaccine trial, IgG responses against the HIV envelope variable loops 1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously reported that infants immunized with an MF59-adjuvanted rgp120 vaccine developed higher-magn ... 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

Correlation Between Anti-gp41 Antibodies and Virus Infectivity Decay During Primary HIV-1 Infection.

Journal article Front Microbiol · 2018 Recent experiments have suggested that the infectivity of simian immunodeficiency virus (SIV) and human immunodeficiency virus type-1 (HIV-1) in plasma decreases over time during primary infection. Because anti-gp41 antibodies are produced early during HIV ... 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

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

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

Computational analysis of antibody dynamics identifies recent HIV-1 infection.

Journal article JCI Insight · December 21, 2017 Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 ant ... Full text Open Access 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

Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs.

Journal article Blood Adv · November 28, 2017 Adjuvants have a critical role for improving vaccine efficacy against many pathogens, including HIV. Here, using transcriptional RNA profiling and systems serology, we assessed how distinct innate pathways altered HIV-specific antibody responses in nonhuma ... Full text Link to item Cite

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

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

DNA Priming Increases Frequency of T-Cell Responses to a Vesicular Stomatitis Virus HIV Vaccine with Specific Enhancement of CD8+ T-Cell Responses by Interleukin-12 Plasmid DNA.

Journal article Clin Vaccine Immunol · November 2017 The HIV Vaccine Trials Network (HVTN) 087 vaccine trial assessed the effect of increasing doses of pIL-12 (interleukin-12 delivered as plasmid DNA) adjuvant on the immunogenicity of an HIV-1 multiantigen (MAG) DNA vaccine delivered by electroporation and b ... Full text Link to item Cite

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

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

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

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

Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice from Ocular Challenge with HSV-1.

Journal article J Virol · October 1, 2017 The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120) construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein D (gD) so that the first 40 amino acids of gp120 were replaced by the signal sequence and the ... Full text Link to item Cite

HIV-1 Consensus Envelope-Induced Broadly Binding Antibodies.

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

Vaccination establishes clonal relatives of germinal center T cells in the blood of humans.

Journal article J Exp Med · July 3, 2017 Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory T cells is less understood. Here, we used ... Full text Link to item Cite

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

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

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

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

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

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

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

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

T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response.

Journal article JCI Insight · April 20, 2017 Humoral immunity is critical for viral control, but the identity and mechanisms regulating human antiviral B cells are unclear. Here, we characterized human B cells expressing T-bet and analyzed their dynamics during viral infections. T-bet+ B cells demons ... Full text Link to item Cite

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

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

Human Epistatic Interaction Controls IL7R Splicing and Increases Multiple Sclerosis Risk.

Journal article Cell · March 23, 2017 Multiple sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7 receptor alpha cha ... Full text Link to item Cite

Humoral and Innate Antiviral Immunity as Tools to Clear Persistent HIV Infection.

Journal article J Infect Dis · March 15, 2017 Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently ... Full text Link to item Cite

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

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

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

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

Immunodominance of Antibody Recognition of the HIV Envelope V2 Region in Ig-Humanized Mice.

Journal article J Immunol · February 1, 2017 In the RV144 gp120 HIV vaccine trial, decreased transmission risk was correlated with Abs that reacted with a linear epitope at a lysine residue at position 169 (K169) in the HIV-1 envelope (Env) V2 region. The K169 V2 response was restricted to Abs bearin ... Full text Link to item Cite

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

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

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

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

Unique cellular and humoral immunogenicity profiles generated by aerosol, intranasal, or parenteral vaccination in rhesus macaques.

Journal article Vaccine · January 23, 2017 Respiratory mucosa immunization is capable of eliciting both local and distal mucosal immune responses; it is a potentially powerful yet largely unused modality for vaccination against respiratory diseases. Targeting the lower versus upper airways by aeros ... Full text Link to item Cite

Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

Journal article PLoS One · 2017 Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to char ... Full text Link to item Cite

Complex immune correlates of protection in HIV-1 vaccine efficacy trials.

Journal article Immunol Rev · January 2017 Development of an efficacious HIV-1 vaccine is a major priority for improving human health worldwide. Vaccine-mediated protection against human pathogens can be achieved through elicitation of protective innate, humoral, and cellular responses. Identificat ... Full text Link to item Cite

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

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

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

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

Structure and Diversity of the Rhesus Macaque Immunoglobulin Loci through Multiple De Novo Genome Assemblies.

Journal article Front Immunol · 2017 The rhesus macaque is a critically important animal model in biomedical research, most recently playing a key role in the development of vaccines against human immunodeficiency virus-1. Nevertheless, the immunoglobulin (Ig) loci of macaques are as yet inco ... Full text Link to item Cite

Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120.

Journal article PLoS One · 2017 Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused ... Full text Link to item Cite

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

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

Envelope-specific antibodies and antibody-derived molecules for treating and curing HIV infection.

Journal article Nat Rev Drug Discov · December 2016 HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

Journal article PLoS Pathog · August 2016 Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the ... Full text Link to item Cite

HIV-1-negative female sex workers sustain high cervical IFNɛ, low immune activation, and low expression of HIV-1-required host genes.

Journal article Mucosal Immunol · July 2016 Sex workers practicing in high HIV endemic areas have been extensively targeted to test anti-HIV prophylactic strategies. We hypothesize that in women with high levels of genital exposure to semen changes in cervico-vaginal mucosal and/or systemic immune a ... Full text Link to item Cite

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

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

Safety and Immunogenicity of a Randomized Phase 1 Prime-Boost Trial With ALVAC-HIV (vCP205) and Oligomeric Glycoprotein 160 From HIV-1 Strains MN and LAI-2 Adjuvanted in Alum or Polyphosphazene.

Journal article J Infect Dis · June 15, 2016 BACKGROUND: Prime-boost regimens comprising ALVAC-HIV (prime) and human immunodeficiency virus type 1 (HIV) Env (boost) induce HIV-specific neutralizing antibody and cell-mediated immune responses, but the impact of boost schedule and adjuvant requires fur ... Full text Link to item Cite

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

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

Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates.

Journal article J Virol · June 1, 2016 UNLABELLED: Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, comb ... Full text Link to item Cite

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

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

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

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

Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel.

Journal article Mucosal Immunol · May 2016 The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and ... Full text Link to item Cite

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

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

Broadly neutralizing antibody specificities detected in the genital tract of HIV-1 infected women.

Journal article AIDS · April 24, 2016 BACKGROUND: Broadly neutralizing antibodies (bNAbs) targeting conserved epitopes on the HIV envelope glycoprotein have been identified in blood from HIV-1 infected women. We investigated whether antibodies in the genital tract from these women share simila ... Full text Link to item Cite

Selection of HIV vaccine candidates for concurrent testing in an efficacy trial.

Journal article Curr Opin Virol · April 2016 Phase IIb or III HIV-1 vaccine efficacy trials are generally large and operationally challenging. To mitigate this challenge, the HIV Vaccine Trials Network is designing a Phase IIb efficacy trial accommodating the evaluation of multiple vaccine regimens c ... Full text Link to item Cite

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

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

CXCL13 is a plasma biomarker of germinal center activity.

Journal article Proc Natl Acad Sci U S A · March 8, 2016 Significantly higher levels of plasma CXCL13 [chemokine (C-X-C motif) ligand 13] were associated with the generation of broadly neutralizing antibodies (bnAbs) against HIV in a large longitudinal cohort of HIV-infected individuals. Germinal centers (GCs) p ... Full text Link to item Cite

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

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

λ Light Chain Bias Associated With Enhanced Binding and Function of Anti-HIV Env Glycoprotein Antibodies.

Journal article J Infect Dis · January 1, 2016 The humoral response to human immunodeficiency virus (HIV) remains incompletely understood. In this report, we describe biased λ light chain use during the HIV Env glycoprotein (Env) response in HIV infection and vaccination. We examined HIV Env binding (a ... Full text Link to item Cite

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

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

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

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

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

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

Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.

Journal article J Immunol · December 15, 2015 Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and i ... Full text Link to item Cite

Immune correlates of vaccine protection against HIV-1 acquisition.

Journal article Sci Transl Med · October 21, 2015 The partial efficacy reported in the RV144 HIV vaccine trial in 2009 has driven the HIV vaccine field to define correlates of risk associated with HIV-1 acquisition and connect these functionally to preventing HIV infection. Immunological correlates, mainl ... Full text Link to item Cite

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

Journal article J Virol · October 2015 UNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatal ... Full text Open Access Link to item Cite

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

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

First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090).

Journal article Open Forum Infect Dis · September 2015 Background.  We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods.  Sixty healthy, HIV-1-uninfect ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

Kernel-based logistic regression model for protein sequence without vectorialization.

Journal article Biostatistics · July 2015 Featured Publication Protein sequence data arise more and more often in vaccine and infectious disease research. These types of data are discrete, high-dimensional, and complex. We propose to study the impact of protein sequences on binary outcomes using a kernel-based logisti ... Full text Link to item Cite

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

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

Structural analysis of the unmutated ancestor of the HIV-1 envelope V2 region antibody CH58 isolated from an RV144 vaccine efficacy trial vaccinee.

Journal article EBioMedicine · July 2015 Human monoclonal antibody CH58 isolated from an RV144 vaccinee binds at Lys169 of the HIV-1 Env gp120 V2 region, a site of vaccine-induced immune pressure. CH58 neutralizes HIV-1 CRF_01 AE strain 92TH023 and mediates ADCC against CD4 + T cell targets infec ... Full text Link to item Cite

COMPASS identifies T-cell subsets correlated with clinical outcomes.

Journal article Nat Biotechnol · June 2015 Advances in flow cytometry and other single-cell technologies have enabled high-dimensional, high-throughput measurements of individual cells as well as the interrogation of cell population heterogeneity. However, in many instances, computational tools to ... Full text Link to item Cite

Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

Journal article J AIDS Clin Res · May 2015 BACKGROUND: Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, ... 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

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 Featured Publication 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

Restricted isotype, distinct variable gene usage, and high rate of gp120 specificity of HIV-1 envelope-specific B cells in colostrum compared with those in blood of HIV-1-infected, lactating African women.

Journal article Mucosal Immunol · March 2015 Featured Publication A successful HIV-1 vaccine must elicit immune responses that impede mucosal virus transmission, though functional roles of protective HIV-1 Envelope (Env)-specific mucosal antibodies remain unclear. Colostrum is a rich source of readily accessible mucosal ... 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 Featured Publication 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

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses.

Journal article PLoS Pathog · February 2015 Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, ... Full text Link to item Cite

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

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

Phase I/II randomized trial of safety and immunogenicity of LIPO-5 alone, ALVAC-HIV (vCP1452) alone, and ALVAC-HIV (vCP1452) prime/LIPO-5 boost in healthy, HIV-1-uninfected adult participants.

Journal article Clin Vaccine Immunol · November 2014 Featured Publication Finding an effective human immunodeficiency virus type 1 (HIV-1) vaccine remains a major global health priority. In a phase I/II, placebo-controlled trial, healthy, HIV-1-negative adults were randomized to receive one of 5 vaccine regimens: LIPO-5 (combina ... Full text Link to item Cite

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

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

Aggregate complexes of HIV-1 induced by multimeric antibodies.

Journal article Retrovirology · October 2, 2014 Featured Publication 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

Transcriptional and posttranscriptional regulation of cytokine gene expression in HIV-1 antigen-specific CD8+ T cells that mediate virus inhibition.

Journal article J Virol · September 1, 2014 Featured Publication UNLABELLED: The ability of CD8+ T cells to effectively limit HIV-1 replication and block HIV-1 acquisition is determined by the capacity to rapidly respond to HIV-1 antigens. Understanding both the functional properties and regulation of an effective CD8+ ... Full text Link to item Cite

FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial.

Journal article J Clin Invest · September 2014 Featured Publication The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1-specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-spec ... Full text Link to item Cite

HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria.

Journal article Cell Host Microbe · August 13, 2014 Featured Publication Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B ce ... Full text Open Access Link to item Cite

Analysis of HLA A*02 association with vaccine efficacy in the RV144 HIV-1 vaccine trial.

Journal article J Virol · August 2014 Featured Publication UNLABELLED: The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31% against HIV-1 infection. Studies into possible correlates of protection found that antibodies specific to the V1 and V2 (V1/V2) region of envelope correlated inversely with infe ... Full text Link to item Cite

Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide.

Journal article J Virol · August 2014 Featured Publication UNLABELLED: Mucosal epithelial cell surface galactosylceramide (Galcer) has been postulated to be a receptor for HIV-1 envelope (Env) interactions with mucosal epithelial cells. Disruption of the HIV-1 Env interaction with such alternate receptors could be ... Full text Link to item Cite

Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles.

Journal article J Infect Dis · July 1, 2014 Featured Publication BACKGROUND: Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected a ... Full text Link to item Cite

HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities.

Journal article J Virol · July 2014 Featured Publication 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

Progress in HIV-1 vaccine development.

Journal article J Allergy Clin Immunol · July 2014 The past 2 years have seen a number of basic and translational science advances in the quest for development of an effective HIV-1 vaccine. These advances include discovery of new envelope targets of potentially protective antibodies, demonstration that CD ... Full text Link to item Cite

Lessons from babies: inducing HIV-1 broadly neutralizing antibodies.

Journal article Nat Med · June 2014 Featured Publication A new study in infants shows that broadly neutralizing antibodies (bNAbs) against HIV can be found early in life, demonstrating for the first time that these antibodies can be induced by the infant immune system. ... Full text Link to item Cite

Capacity for infectious HIV-1 virion capture differs by envelope antibody specificity.

Journal article J Virol · May 2014 Featured Publication Antibody capacity to recognize infectious virus is a prerequisite of many antiviral functions. We determined the infectious virion capture index (IVCI) of different antibody specificities. Whereas broadly neutralizing antibodies (bNAbs), except for an MPER ... Full text Link to item Cite

High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes.

Journal article Sci Rep · April 23, 2014 Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide e ... Full text Link to item Cite

An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1.

Journal article J Clin Invest · April 2014 Featured Publication Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnA ... Full text Link to item Cite

Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination.

Journal article Sci Transl Med · March 19, 2014 Featured Publication HIV-1-specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass pro ... Full text Link to item Cite

Toll-like receptor 7/8 (TLR7/8) and TLR9 agonists cooperate to enhance HIV-1 envelope antibody responses in rhesus macaques.

Journal article J Virol · March 2014 Featured Publication UNLABELLED: The development of a vaccine that can induce high titers of functional antibodies against HIV-1 remains a high priority. We have developed an adjuvant based on an oil-in-water emulsion that incorporates Toll-like receptor (TLR) ligands to test ... Full text Link to item Cite

Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune Correlates.

Journal article Vaccines (Basel) · March 2014 Featured Publication Interrogating immune correlates of infection risk for efficacious and non-efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the mechanisms of induction of protective immunity to HIV-1. To date, there have been six HIV-1 vaccine e ... Full text Link to item Cite

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

Journal article Nature · January 23, 2014 Featured Publication 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

Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.

Journal article PLoS One · 2014 Featured Publication UNLABELLED: In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cros ... Full text Link to item Cite

IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.

Journal article PLoS One · 2014 B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, ... Full text Open Access Link to item Cite

DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques.

Journal article PLoS One · 2014 We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and m ... Full text Link to item Cite

Reconstructing a B-Cell Clonal Lineage. II. Mutation, Selection, and Affinity Maturation.

Journal article Front Immunol · 2014 Affinity maturation of the antibody response is a fundamental process in adaptive immunity during which B-cells activated by infection or vaccination undergo rapid proliferation accompanied by the acquisition of point mutations in their rearranged immunogl ... Full text Open Access Link to item Cite

HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

Journal article PLoS One · 2014 BACKGROUND: Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to prote ... Full text Link to item Cite

Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine.

Journal article N Engl J Med · November 28, 2013 Featured Publication BACKGROUND: A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at in ... Full text Link to item Cite

Vaccination with Vaxfectin(®) adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia.

Journal article Hum Vaccin Immunother · October 2013 Featured Publication 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

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 Featured Publication 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

Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking.

Journal article J Virol · September 2013 Featured Publication Experimental vaccine antigens based upon the HIV-1 envelope glycoproteins (Env) have failed to induce neutralizing antibodies (NAbs) against the majority of circulating viral strains as a result of antibody evasion mechanisms, including amino acid variabil ... Full text Link to item Cite

HIV-1 gp41 envelope IgA is frequently elicited after transmission but has an initial short response half-life.

Journal article Mucosal Immunol · July 2013 Featured Publication Prevention of HIV-1 transmission at mucosal surfaces will likely require durable pre-existing mucosal anti-HIV-1 antibodies (Abs). Defining the ontogeny, specificities and potentially protective nature of the initial mucosal virus-specific B-cell response ... Full text Link to item Cite

Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees.

Journal article J Virol · July 2013 Featured Publication The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent a ... Full text Open Access Link to item Cite

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 Featured Publication We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody respon ... Full text Link to item Cite

Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG.

Journal article Proc Natl Acad Sci U S A · May 28, 2013 Featured Publication Analysis of correlates of risk of infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas HIV-1 Env-specific plasma IgA responses dire ... Full text Link to item Cite

Quality control, analysis and secure sharing of Luminex® immunoassay data using the open source LabKey Server platform.

Journal article BMC Bioinformatics · April 30, 2013 Featured Publication BACKGROUND: Immunoassays that employ multiplexed bead arrays produce high information content per sample. Such assays are now frequently used to evaluate humoral responses in clinical trials. Integrated software is needed for the analysis, quality control, ... Full text Link to item Cite

DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge.

Journal article Proc Natl Acad Sci U S A · February 19, 2013 Featured Publication We have previously shown that macaques vaccinated with DNA vectors expressing SIVmac239 antigens developed potent immune responses able to reduce viremia upon high-dose SIVmac251 challenge. To further improve vaccine-induced immunity and protection, we com ... Full text Link to item Cite

Antigenicity and immunogenicity of RV144 vaccine AIDSVAX clade E envelope immunogen is enhanced by a gp120 N-terminal deletion.

Journal article J Virol · February 2013 An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-am ... Full text Link to item Cite

Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

Journal article J Virol · February 2013 Featured Publication The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the l ... Full text Link to item Cite

Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.

Journal article Immunity · January 24, 2013 Featured Publication The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial ... Full text Link to item Cite

Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial.

Journal article PLoS One · 2013 Featured Publication The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B and E) was previously shown to have a 31.2% efficacy rate. Plasma specimens from vaccine and placebo recipients were use ... Full text Link to item Cite

Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial.

Journal article PLoS One · 2013 Featured Publication Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced protection. Here, plasma IgG responses were assessed in three ... Full text Link to item Cite

HIV-1 antibodies from infection and vaccination: insights for guiding vaccine design.

Journal article Trends Microbiol · November 2012 Attempts to formulate a protective HIV-1 vaccine through classic vaccine design strategies have not been successful. Elicitation of HIV-1-specific broadly neutralizing antibodies (bnAbs) at high titers that are present before exposure might be required to ... Full text Link to item Cite

The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120.

Journal article AIDS Res Hum Retroviruses · November 2012 The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antib ... Full text Link to item Cite

Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family.

Journal article J Virol · November 2012 The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytoto ... Full text Link to item Cite

CD4 T follicular helper cell dynamics during SIV infection.

Journal article J Clin Invest · September 2012 CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation ... Full text Link to item Cite

The development of CD4 binding site antibodies during HIV-1 infection.

Journal article J Virol · July 2012 Broadly neutralizing antibodies to the CD4 binding site (CD4bs) of gp120 are generated by some HIV-1-infected individuals, but little is known about the prevalence and evolution of this antibody response during the course of HIV-1 infection. We analyzed th ... Full text Link to item Cite

HIV-1 gp120 vaccine induces affinity maturation in both new and persistent antibody clonal lineages.

Journal article J Virol · July 2012 Most antibodies that broadly neutralize HIV-1 are highly somatically mutated in antibody clonal lineages that persist over time. Here, we describe the analysis of human antibodies induced during an HIV-1 vaccine trial (GSK PRO HIV-002) that used the clade ... Full text Link to item Cite

Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication.

Journal article J Virol · June 2012 CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8(+) T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8(+) responses t ... Full text Open Access Link to item Cite

CD4+CD8+ T cells represent a significant portion of the anti-HIV T cell response to acute HIV infection.

Journal article J Immunol · May 1, 2012 Previous studies have revealed that HIV-infected individuals possess circulating CD4(+)CD8(+) double-positive (DP) T cells specific for HIV Ags. In the present study, we analyzed the proliferation and functional profile of circulating DP T cells from 30 ac ... Full text Link to item Cite

Immune-correlates analysis of an HIV-1 vaccine efficacy trial.

Journal article N Engl J Med · April 5, 2012 BACKGROUND: In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. METHODS: ... Full text Link to item Cite

116 Autologous and Heterologous Neutralizing Antibody Responses in HIV-1 Infection

Journal article JAIDS Journal of Acquired Immune Deficiency Syndromes · April 2012 Full text Cite

Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design.

Journal article J Virol · April 2012 Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from ... Full text Open Access Link to item Cite

Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge.

Journal article Mucosal Immunol · January 2012 Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus. We aimed to generate strong mucosal immune responses to simian immunodeficiency virus (SIV) in rhesus maca ... Full text Link to item Cite

Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.

Journal article PLoS One · 2012 BACKGROUND: Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody respo ... Full text Open Access Link to item Cite

Timing of plasmid cytokine (IL-2/Ig) administration affects HIV-1 vaccine immunogenicity in HIV-seronegative subjects.

Journal article J Infect Dis · November 15, 2011 BACKGROUND: To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig). M ... Full text Link to item Cite

Multiple HIV-1-specific IgG3 responses decline during acute HIV-1: implications for detection of incident HIV infection.

Journal article AIDS · November 13, 2011 Featured Publication OBJECTIVE: Different HIV-1 antigen specificities appear in sequence after HIV-1 transmission and the immunoglobulin G (IgG) subclass responses to HIV antigens are distinct from each other. The initial predominant IgG subclass response to HIV-1 infection co ... Full text Open Access Link to item Cite

Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals.

Journal article J Virol · November 2011 Featured Publication A small proportion of HIV-infected individuals generate a neutralizing antibody (NAb) response of exceptional magnitude and breadth. A detailed analysis of the critical epitopes targeted by broadly neutralizing antibodies should help to define optimal targ ... Full text Link to item Cite

Dynamic antibody specificities and virion concentrations in circulating immune complexes in acute to chronic HIV-1 infection.

Journal article J Virol · November 2011 Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent tr ... Full text Link to item Cite

Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation.

Journal article J Virol · November 2011 Genetic factors, as well as antigenic stimuli, can influence antibody repertoire formation. Moreover, the affinity of antigen for unmutated naïve B cell receptors determines the threshold for activation of germinal center antibody responses. The gp41 2F5 b ... Full text Link to item Cite

Cross-reactive HIV-1-neutralizing human monoclonal antibodies identified from a patient with 2F5-like antibodies.

Journal article J Virol · November 2011 The genes encoding broadly HIV-1-neutralizing human monoclonal antibodies (MAbs) are highly divergent from their germ line counterparts. We have hypothesized that such high levels of somatic hypermutation could pose a challenge for elicitation of the broad ... Full text Link to item Cite

Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.

Journal article J Exp Med · October 24, 2011 The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we ... Full text Open Access Link to item Cite

Primary infection by a human immunodeficiency virus with atypical coreceptor tropism.

Journal article J Virol · October 2011 Featured Publication The great majority of human immunodeficiency virus type 1 (HIV-1) strains enter CD4+ target cells by interacting with one of two coreceptors, CCR5 or CXCR4. Here we describe a transmitted/founder (T/F) virus (ZP6248) that was profoundly impaired in its abi ... Full text Link to item Cite

Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors.

Journal article J Virol · October 2011 V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificit ... Full text Link to item Cite

HIV-DNA priming alters T cell responses to HIV-adenovirus vaccine even when responses to DNA are undetectable.

Journal article J Immunol · September 15, 2011 Featured Publication Many candidate HIV vaccines are designed to primarily elicit T cell responses. Although repeated immunization with the same vaccine boosts Ab responses, the benefit for T cell responses is ill defined. We compared two immunization regimens that include the ... Full text Link to item Cite

HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies.

Journal article J Virol · September 2011 Despite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies ... Full text Open Access Link to item Cite

Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.

Journal article PLoS Pathog · September 2011 Here we have identified HIV-1 B clade Envelope (Env) amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To ac ... Full text Link to item Cite

Envelope deglycosylation enhances antigenicity of HIV-1 gp41 epitopes for both broad neutralizing antibodies and their unmutated ancestor antibodies.

Journal article PLoS Pathog · September 2011 The HIV-1 gp41 envelope (Env) membrane proximal external region (MPER) is an important vaccine target that in rare subjects can elicit neutralizing antibodies. One mechanism proposed for rarity of MPER neutralizing antibody generation is lack of reverted u ... Full text Link to item Cite

Isolation of a monoclonal antibody that targets the alpha-2 helix of gp120 and represents the initial autologous neutralizing-antibody response in an HIV-1 subtype C-infected individual.

Journal article J Virol · August 2011 Featured Publication The C3-V4 region is a major target of autologous neutralizing antibodies in HIV-1 subtype C infection. We previously identified a Center for AIDS Program of Research in South Africa (CAPRISA) participant, CAP88, who developed a potent neutralizing-antibody ... Full text Link to item Cite

High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses.

Journal article Cytometry A · August 2011 We have developed a high-throughput platform to detect the presence of HIV-1 and SIV-specific ADCC-mediating antibody responses. The assay is based on the hydrolysis of a cell-permeable fluorogenic peptide substrate containing a sequence recognized by the ... Full text Link to item Cite

An HIV-1 gp120 envelope human monoclonal antibody that recognizes a C1 conformational epitope mediates potent antibody-dependent cellular cytotoxicity (ADCC) activity and defines a common ADCC epitope in human HIV-1 serum.

Journal article J Virol · July 2011 Featured Publication Among nonneutralizing HIV-1 envelope antibodies (Abs), those capable of mediating antibody-dependent cellular cytotoxicity (ADCC) activity have been postulated to be important for control of HIV-1 infection. ADCC-mediating Ab must recognize HIV-1 antigens ... Full text Link to item Cite

Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates.

Journal article Proc Natl Acad Sci U S A · April 26, 2011 Featured Publication Protein vaccines, if rendered immunogenic, would facilitate vaccine development against HIV and other pathogens. We compared in nonhuman primates (NHPs) immune responses to HIV Gag p24 within 3G9 antibody to DEC205 ("DEC-HIV Gag p24"), an uptake receptor o ... Full text Link to item Cite

A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.

Journal article J Infect Dis · April 15, 2011 Featured Publication BACKGROUND: A key missing element in the development of a successful human immunodeficiency virus (HIV) vaccine is an immunogen that can generate broadly cross-neutralizing antibodies against primary isolates of the virus. METHODS: This phase 1 clinical tr ... Full text Link to item Cite

CD8(+)T-cell-mediated control of HIV-1 and SIV infection.

Journal article Immunol Res · April 2011 Featured Publication A detailed understanding of the cellular response to human immunodeficiency virus (HIV-1) infection is needed to inform prevention and therapeutic strategies that aim to contain the AIDS pandemic. The cellular immune response plays a critical role in reduc ... Full text Link to item Cite

Alterations of the B-cell response by HIV-1 replication.

Journal article Curr HIV/AIDS Rep · March 2011 Featured Publication While the hallmark of HIV-1 infection is the progressive depletion of CD4(+) T cells, extensive B-cell dysfunction ensues that impairs the quality of the humoral response. HIV-1 infection causes hypergammaglobulinemia, polyclonal activation, loss of memory ... Full text Link to item Cite

Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles.

Journal article J Infect Dis · March 1, 2011 Featured Publication BACKGROUND: Recombinant DNA and modified vaccinia virus Ankara (rMVA) vaccines represent a promising approach to an HIV/AIDS vaccine. This Phase 1 clinical trial compared the safety and immunogenicity of a rMVA vaccine administered with and without DNA vac ... Full text Link to item Cite

A phase I trial of preventive HIV vaccination with heterologous poxviral-vectors containing matching HIV-1 inserts in healthy HIV-uninfected subjects.

Journal article Vaccine · February 24, 2011 Featured Publication We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara [MVA] and fowlpox [FPV]) in a homologous and heterologous vector prime-boost vaccination regimen containing matching HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 ... Full text Link to item Cite

Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.

Journal article PLoS Pathog · February 10, 2011 In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus es ... Full text Link to item Cite

B cell responses to HIV-1 infection and vaccination: pathways to preventing infection.

Journal article Trends Mol Med · February 2011 Featured Publication The B cell arm of the immune response becomes activated soon after HIV-1 transmission, yet the initial antibody response does not control HIV-1 replication, and it takes months for neutralizing antibodies to develop against the autologous virus. Antibodies ... Full text Link to item Cite

A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204).

Journal article PLoS One · 2011 Featured Publication BACKGROUND: The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegativ ... Full text Link to item Cite

Safety and immunogenicity of an HIV adenoviral vector boost after DNA plasmid vaccine prime by route of administration: a randomized clinical trial.

Journal article PLoS One · 2011 BACKGROUND: In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor. METHODOLOGY/PRINCIPAL FINDINGS: This multicenter, open-label, randomized trial, HVTN 069, com ... Full text Link to item Cite

Secretion of MIP-1β and MIP-1α by CD8(+) T-lymphocytes correlates with HIV-1 inhibition independent of coreceptor usage.

Journal article Cell Immunol · 2011 CD8(+) T-lymphocytes can utilize noncytolytic mechanisms to suppress HIV-1 replication through the secretion of soluble factors. The secretion of MIP-1β, MIP-1α, IP-10, MIG, IL-1α, and interferon gamma correlated most strongly with soluble noncytolytic sup ... Full text Link to item Cite

H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

Journal article PLoS One · 2011 Featured Publication BACKGROUND: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal ... Full text Open Access Link to item Cite

Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41.

Journal article PLoS One · 2011 Featured Publication A component to the problem of inducing broad neutralizing HIV-1 gp41 membrane proximal external region (MPER) antibodies is the need to focus the antibody response to the transiently exposed MPER pre-hairpin intermediate neutralization epitope. Here we des ... Full text Link to item Cite

Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.

Journal article PLoS One · 2011 Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP ... Full text Link to item Cite

Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054).

Journal article PLoS One · October 27, 2010 BACKGROUND: Individuals without prior immunity to a vaccine vector may be more sensitive to reactions following injection, but may also show optimal immune responses to vaccine antigens. To assess safety and maximal tolerated dose of an adenoviral vaccine ... Full text Open Access Link to item Cite

Low-dose mucosal simian immunodeficiency virus infection restricts early replication kinetics and transmitted virus variants in rhesus monkeys.

Journal article J Virol · October 2010 Defining the earliest virologic events following human immunodeficiency virus type 1 (HIV-1) transmission may be critical for the design of vaccine strategies aimed at blocking acquisition of HIV-1 infection. In particular, the length of the eclipse phase ... Full text Link to item Cite

Epigenetic regulation of CD8(+) T-lymphocyte mediated suppression of HIV-1 replication.

Journal article Virology · September 15, 2010 CD8(+) T-lymphocytes from HIV-1 infected individuals express unidentified factors that suppress viral replication by inhibiting HIV-1 gene expression. We examined the role of epigenetics in modulating the HIV-1 suppressive factors expressed by primary CD8( ... Full text Link to item Cite

Strategies for eliciting HIV-1 inhibitory antibodies.

Journal article Curr Opin HIV AIDS · September 2010 PURPOSE OF REVIEW: Major roadblocks persist in the development of vaccines that elicit potent neutralizing antibodies targeting diverse HIV-1 strains, similar to known broadly neutralizing HIV-1 human monoclonal antibodies. Alternatively, other types of an ... Full text Link to item Cite

Is developing an HIV-1 vaccine possible?

Journal article Curr Opin HIV AIDS · September 2010 PURPOSE OF REVIEW: This review discusses select recent data that suggest that indeed it is possible to make a clinically useful preventive vaccine for HIV-1 and outlines some of the remaining obstacles that stand in the way of success. RECENT FINDINGS: Pas ... Full text Link to item Cite

Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination.

Journal article J Virol · May 2010 Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8(+) T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8(+) T cells capable of this activity ... Full text Open Access Link to item Cite

Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce beta-chemokines.

Journal article J Exp Med · April 12, 2010 Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. ... Full text Open Access Link to item Cite

Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution.

Journal article Proc Natl Acad Sci U S A · March 30, 2010 The conserved membrane-proximal external region (MPER) of HIV-1 envelope is a target for the rare broadly neutralizing 2F5, Z13, and 4E10 monoclonal antibodies (mAbs). One strategy to elicit such antibodies is to design an immunogen with increased exposure ... Full text Link to item Cite

Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1.

Journal article Virology · January 20, 2010 Neutralizing antibody (nAb) response is sporadic and has limited potency and breadth during infection with human immunodeficiency virus type 1 (HIV-1). In rare cases, broad and potent nAbs are actually induced in vivo. Identifying specific epitopes targete ... Full text Link to item Cite

The immune response during acute HIV-1 infection: clues for vaccine development.

Journal article Nat Rev Immunol · January 2010 The early immune response to HIV-1 infection is likely to be an important factor in determining the clinical course of disease. Recent data indicate that the HIV-1 quasispecies that arise following a mucosal infection are usually derived from a single tran ... Full text Link to item Cite

Cross-reactive monoclonal antibodies to multiple HIV-1 subtype and SIVcpz envelope glycoproteins.

Journal article Virology · November 10, 2009 The extraordinarily high level of genetic variation of HIV-1 env genes poses a challenge to obtain antibodies that cross-react with multiple subtype Env glycoproteins. To determine if cross-reactive monoclonal antibodies (mAbs) to highly conserved epitopes ... Full text Link to item Cite

HIV-1-specific antibody responses during acute and chronic HIV-1 infection.

Journal article Curr Opin HIV AIDS · September 2009 PURPOSE OF REVIEW: The humoral immune response to HIV-1 throughout infection is comprised of complex mixtures of antibody isotypes with numerous HIV-1 specificities. However, unlike antibody responses to most infections, protective antibody responses are d ... Full text Link to item Cite

Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors.

Journal article J Virol · September 2009 Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1- ... Full text Link to item Cite

Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection.

Journal article PLoS Med · July 7, 2009 BACKGROUND: The antibody response to HIV-1 does not appear in the plasma until approximately 2-5 weeks after transmission, and neutralizing antibodies to autologous HIV-1 generally do not become detectable until 12 weeks or more after transmission. Moreove ... Full text Open Access Link to item Cite

Vaccination with vif-deleted feline immunodeficiency virus provirus, GM-CSF, and TNF-alpha plasmids preserves global CD4 T lymphocyte function after challenge with FIV.

Journal article Vaccine · June 8, 2009 Feline immunodeficiency virus (FIV) DNA vaccine approaches that included a vif-deleted FIV provirus (FIV-pPPRDeltavif) and feline cytokine expression plasmids were tested for immunogenicity and efficacy by immunization of specific pathogen free cats. Vacci ... Full text Link to item Cite

Tat-SF1 is not required for Tat transactivation but does regulate the relative levels of unspliced and spliced HIV-1 RNAs.

Journal article PLoS One · May 27, 2009 BACKGROUND: HIV-1 relies on several host proteins for productive viral transcription. HIV-1 Tat-specific factor 1 (Tat-SF1) is among these cofactors that were identified by in vitro reconstituted transcription reactions with immunodepleted nuclear extracts ... Full text Link to item Cite

Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers.

Journal article AIDS · May 15, 2009 OBJECTIVE: To determine the spectrum of antiviral antibodies in HIV-1-infected individuals in whom viral replication is spontaneously undetectable, termed HIV controllers (HICs). DESIGN: Multicenter French trial ANRS EP36 studying the viral control in HICs ... Full text Link to item Cite

In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth.

Journal article J Virol · April 2009 The broadly neutralizing human monoclonal antibodies (MAbs) 2F5 and 4E10, both targeting the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope membrane proximal external region (MPER), are among the MAbs with the broadest heterologous n ... Full text Link to item Cite

Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia.

Journal article J Virol · December 2008 A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune resp ... Full text Link to item Cite

Profiling the specificity of neutralizing antibodies in a large panel of plasmas from patients chronically infected with human immunodeficiency virus type 1 subtypes B and C.

Journal article J Virol · December 2008 Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigat ... Full text Link to item Cite

Improving peptide-MHC class I binding prediction for unbalanced datasets.

Journal article BMC Bioinformatics · September 19, 2008 BACKGROUND: Establishment of peptide binding to Major Histocompatibility Complex class I (MHCI) is a crucial step in the development of subunit vaccines and prediction of such binding could greatly reduce costs and accelerate the experimental process of id ... Full text Link to item Cite

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.

Journal article Proc Natl Acad Sci U S A · May 27, 2008 The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathe ... Full text Link to item Cite

Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection.

Journal article J Virol · January 2008 Two human monoclonal antibodies (MAbs) (2F5 and 4E10) against the human immunodeficiency virus type 1 (HIV-1) envelope g41 cluster II membrane proximal external region (MPER) broadly neutralize HIV-1 primary isolates. However, these antibody specificities ... Full text Link to item Cite

Lessons from a multisite international trial in the Caribbean and South America of an HIV-1 Canarypox vaccine (ALVAC-HIV vCP1452) with or without boosting with MN rgp120.

Journal article J Acquir Immune Defic Syndr · October 1, 2007 BACKGROUND: The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial eva ... Full text Link to item Cite

A feline immunodeficiency virus vif-deletion mutant remains attenuated upon infection of newborn kittens.

Journal article J Gen Virol · October 2007 This report characterizes lentivirus attenuation associated with a vif mutation by inoculation of newborn kittens with a vif-deleted feline immunodeficiency virus provirus plasmid (FIV-pPPRDeltavif). Virus in peripheral blood, antiviral antibody or CD4 T-c ... Full text Link to item Cite

Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial.

Journal article J Acquir Immune Defic Syndr · February 1, 2007 BACKGROUND: A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp12 ... Full text Link to item Cite

Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers.

Journal article Vaccine · January 5, 2007 BACKGROUND: Use of the recombinant proteins NefTat and gp120(W61D) formulated with the AS02A adjuvant system was previously shown to protect against AIDS in a rhesus macaque SHIV animal model system. METHODS: Eighty-four HIV uninfected human participants w ... Full text Link to item Cite

Initiation of human immunodeficiency virus type 1 (HIV-1) transcription is inhibited by noncytolytic CD8 suppression.

Journal article Open Virol J · 2007 The replication of human immunodeficiency virus type 1 (HIV-1) can be inhibited by noncytolytic CD8(+) T cell mediated suppression, an immune response that specifically targets HIV-1 gene expression. Clinical studies demonstrate that this immune response m ... Full text Link to item Cite

HIV-1 vaccine induced immune responses in newborns of HIV-1 infected mothers.

Journal article AIDS · July 13, 2006 OBJECTIVE: Breast milk transmission continues to account for a large proportion of cases of mother-to-child transmission of HIV-1 worldwide. An effective HIV-1 vaccine coupled with either passive immunization or short-term antiretroviral prophylaxis repres ... Full text Link to item Cite

Safety and immunogenicity of an HIV-1 recombinant canarypox vaccine in newborns and infants of HIV-1-infected women.

Journal article J Infect Dis · December 15, 2005 Pediatric AIDS Clinical Trials Group protocol 326 is a study of 2 formulations of recombinant canarypox ALVAC vaccine (vCP205) against human immunodeficiency virus type 1 (HIV-1). HIV-1-exposed infants were randomized to receive 1 of 2 formulations of vCP2 ... Full text Link to item Cite

High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects.

Journal article J Infect Dis · October 1, 2005 BACKGROUND: In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was cond ... Full text Link to item Cite

Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection.

Journal article Proc Natl Acad Sci U S A · March 22, 2005 Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we ex ... Full text Link to item Cite

Longitudinal assessment of immune response and viral characteristics in HIV-infected patients with prolonged CD4(+)/viral load discordance.

Journal article AIDS Res Hum Retroviruses · January 2005 Although suppression of HIV-1 RNA below the limit of detection is associated with optimal outcomes, many patients can maintain or increase their CD4(+) count for prolonged time periods in the presence of persistent low-level viremia. We followed seven pati ... Full text Link to item Cite

Rapid clearance of virus after acute HIV-1 infection: correlates of risk of AIDS.

Journal article J Infect Dis · May 15, 2004 OBJECTIVE: Our objective was to define early virologic and immunologic determinants of human immunodeficiency virus (HIV) type 1 disease progression among 22 case subjects with acute infection from the Trinidad Seroconvertor Cohort. METHODS: A linear segme ... Full text Link to item Cite

The effects of HHV-8 vMIP-II on SIVmac251 infection and replication competent and incompetent SIVmac239Delta3 vectors.

Journal article Virus Res · August 2003 Human herpesvirus type 8 vMIP-II has one of the broadest ranges of chemokine receptor binding and therefore a multiplicity of biologic effects, both immunologic and antiviral. These properties make vMIP-II an attractive effector gene to be expressed from g ... Full text Link to item Cite

Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control.

Journal article J Infect Dis · April 1, 2003 Mechanisms that underly discordant CD4+ cell/virus load (VL) responses in patients who receive highly active antiretroviral therapy (HAART) were studied in 30 human immunodeficiency virus (HIV)-positive patients, in 3 groups. Discordant responders maintain ... Full text Link to item Cite

CD8+ T cell mediated noncytolytic inhibition of human immunodeficiency virus type I.

Journal article Front Biosci · March 1, 2001 The development of cellular immune responses in primary human immunodeficiency virus type-1 (HIV-1) infection is accompanied by a dramatic decrease in plasma viremia and resolution of the acute clinical syndrome. The full nature of the immunological respon ... Full text Link to item Cite

Mechanisms for HIV-1 Entry: Current Strategies to Interfere with This Step.

Journal article Curr Infect Dis Rep · February 2001 Striking reductions in HIV replication, in vivo, by potent combinations of antiretroviral therapies (ART) are the most significant contributor to the decline in HIV morbidity and mortality. Unfortunately, HIV is not eradicated and rebounds quickly when the ... Full text Link to item Cite

Identification of ENV determinants in V3 that influence the molecular anatomy of CCR5 utilization.

Journal article J Mol Biol · September 15, 2000 The V3 loop of the ENV glycoprotein exerts a dominant influence on the interaction of gp120 with coreceptors. Primary env genes cloned from sequential isolates from two seroconverters revealed Pro-->Ala conversion in the conserved GPG motif of the V3 crown ... Full text Link to item Cite

CD8+ T cell-mediated suppressive activity inhibits HIV-1 after virus entry with kinetics indicating effects on virus gene expression.

Journal article Proc Natl Acad Sci U S A · March 28, 2000 Individuals infected with HIV-1 have varying rates of progression to AIDS. Cellular immune responses, comprised of cytolytic and noncytolytic CD8(+) T cell effector functions, are considered important for controlling viremia and maintaining the clinically ... Full text Link to item Cite

ETS transcription factors regulate an enhancer activity in the third intron of TNF-alpha.

Journal article J Leukoc Biol · July 1999 We describe an enhancer site in the third intron of tumor necrosis factor alpha (TNF-alpha). A reporter construct containing the 5'-flanking region of the mouse TNF-alpha gene displayed weak activity when transfected into RAW264.7 macrophage-like cells. Th ... Full text Link to item Cite

Two forms of NF-kappa B1 (p105/p50) in murine macrophages: differential regulation by lipopolysaccharide, interleukin-2, and interferon-gamma.

Journal article J Interferon Cytokine Res · May 1997 In macrophages, nuclear factor kappa B (NF-kappa B) has been shown to transactivate the promoters of many cytokines, including tumor necrosis factor-alpha (TNF-alpha). We have used the -510 kappa B binding site from the murine TNF-alpha promoter to assay t ... Full text Link to item Cite