Scholars@Duke
Guido Ferrari

Guido Ferrari

Professor in Surgery
Surgery, Surgical Sciences
gflmp@duke.edu
Box 2926 Med Ctr, Durham, NC 27710
915 S. LaSalle Street, SORF Building Room 208, Durham, NC 27710
Office hours Monday-Friday 08:00-18:00
Saturday and Sunday upon request  

Selected Publications

Decreased variability in the site-specific results during participation in the External Quality Assurance Program Oversight Laboratory (EQAPOL) proficiency program for IFN-gamma enzyme-linked immunospot (IFN-γ ELISpot) assay.

Journal Article Journal of immunological methods · November 2024 The NIAID DAIDS-sponsored External Quality Assurance Program Oversight Laboratory (EQAPOL) manages an interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) external proficiency program. The ELISpot program evaluates the accuracy and variability of re ... Full text 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 Link to item Cite

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

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

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

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

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

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

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

A remarkable genetic shift in a transmitted/founder virus broadens antibody responses against HIV-1.

Journal Article Elife · April 15, 2024 A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine shou ... Full text Link to item Cite

A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals.

Journal Article medRxiv · March 18, 2024 BACKGROUND: HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccin ... 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

A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions.

Journal Article PLoS One · 2024 To eliminate vertical HIV transmission and achieve therapy-free viral suppression among children living with HIV, novel strategies beyond antiretroviral therapy (ART) are necessary. Our group previously identified a triple broadly neutralizing antibody (bN ... Full text Link to item Cite

Methods for Evaluating Antigen-Specific Cytotoxic T Lymphocyte Frequency and Activity

Chapter · January 1, 2024 Antigen-specific Cytotoxic T Lymphocytes (CTLs) can be detected by measuring responsiveness to major histocompatibility complex class I (MHC-I)-presented peptide as the ability to produce cytokines/chemokines or to eliminate target cells. Functional assays ... Full text Cite

Methods for Detection of Antigen-Specific T Cells by Enzyme-Linked Immunospot Assay

Chapter · January 1, 2024 The enzyme-linked immunospot (ELISPOT) assay to detect T cell responses was developed based on the initial technique reported by Czerkinsky et al. in 1983 as an alternative to the plaque-forming assay for the detection of antibody-secreting cells. In an ef ... Full text Cite

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

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

Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.

Journal Article bioRxiv · November 11, 2023 A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in pl ... 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

AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques.

Journal Article Nat Med · October 2023 The main barrier to HIV cure is a persistent reservoir of latently infected CD4+ T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach to target this reservoir involve ... Full text Link to item Cite

Engineered Immunogens to Elicit Antibodies Against Conserved Coronavirus Epitopes.

Journal Article bioRxiv · September 17, 2023 Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815 ... Full text Link to item Cite

HIV specific Th1 responses are altered in Ugandans with HIV and Schistosoma mansoni coinfection.

Journal Article BMC Immunol · August 29, 2023 BACKGROUND: Fishing communities surrounding Lake Victoria in Uganda have HIV prevalence of 28% and incidence rates of 5 per 100 person years. More than 50% of the local fishermen are infected with Schistosoma mansoni (S. mansoni). We investigated the role ... Full text Link to item Cite

Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability.

Journal Article AIDS · August 1, 2023 OBJECTIVES: The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a nonneutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen on ... 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

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

Validation of the performance and suitability of a new class of FBS optimized for use in single-cell functional assays.

Journal Article J Immunol Methods · April 2023 The use of conventional serum for supplementation of media in cell-based and single-cell functional assays has been a major challenge for assay performance, standardization, optimization, and reproducibility. It has been identified as the leading cause of ... Full text Link to item Cite

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

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

Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies.

Journal Article J Virol · February 28, 2023 Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the ... Full text Link to item Cite

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

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

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

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

Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses.

Journal Article Immunogenetics · February 2023 Heritable polymorphisms within the human IgG locus, collectively termed allotypes, have often been linked by statistical associations, but rarely mechanistically, to a wide range of disease states. One potential explanation for these associations is that I ... Full text Link to item Cite

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

Conference Frontiers in Immunology · January 1, 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 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

Expression of membrane Hsp90 is a molecular signature of T cell activation.

Journal Article Sci Rep · October 27, 2022 Heat shock protein 90 (Hsp90) maintains cellular proteostasis during stress and has been under investigation as a therapeutic target in cancer for over two decades. We and others have identified a membrane expressed form of Hsp90 (mHsp90) that previously a ... Full text Link to item Cite

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

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

Single-cell analysis of immune cell transcriptome during HIV-1 infection and therapy.

Journal Article BMC Immunol · September 29, 2022 BACKGROUND: Cellular immune responses are phenotypically and functionally perturbed during HIV-1 infection, with the majority of function restored upon antiretroviral therapy (ART). Despite ART, residual inflammation remains that can lead to HIV-related co ... Full text Link to item Cite

Bispecific antibody-derived molecules to target persistent HIV infection.

Journal Article J Virus Erad · September 2022 HIV infection persists despite durable and potent antiviral therapy. To target persistent HIV infection, one major strategy aims to induce HIV provirus expression using latency reversing agents and then eliminate these reservoir cells via immune responses ... Full text Link to item Cite

High Asymptomatic Carriage With the Omicron Variant in South Africa.

Journal Article Clin Infect Dis · August 24, 2022 We report a 23% asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T- ... 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

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

Cellular immune assays for evaluation of vaccine efficacy

Chapter · June 1, 2022 A greater understanding of the immune response, particularly of cell-mediated immune responses in malaria, tuberculosis (TB), human immunodeficiency virus (HIV), and cancer patients, will lead to improved vaccine design. Currently, in vitro analyses of cel ... Full text Cite

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

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

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

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

Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.

Journal Article Commun Biol · March 28, 2022 The non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-media ... Full text Link to item Cite

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

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

Vaccine-Induced, High-Magnitude HIV Env-Specific Antibodies with Fc-Mediated Effector Functions Are Insufficient to Protect Infant Rhesus Macaques against Oral SHIV Infection.

Journal Article mSphere · February 23, 2022 Improved access to antiretroviral therapy (ART) and antenatal care has significantly reduced in utero and peripartum mother-to-child human immunodeficiency virus (HIV) transmission. However, as breast milk transmission of HIV still occurs at an unacceptabl ... Full text Link to item Cite

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

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

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

Anti-HIV antibody development up to 1 year after antiretroviral therapy initiation in acute HIV infection.

Journal Article J Clin Invest · January 4, 2022 Early initiation of antiretroviral therapy (ART) in acute HIV infection (AHI) is effective at limiting seeding of the HIV viral reservoir, but little is known about how the resultant decreased antigen load affects long-term Ab development after ART. We rep ... 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

CD8 depletion and N-803 plus anti-SIV Env RhmAbs in ART-suppressed rhesus macaques

Conference JOURNAL OF THE INTERNATIONAL AIDS SOCIETY · 2022 Cite

Immune correlates analysis of the Imbokodo HIV-1 vaccine efficacy trial

Conference JOURNAL OF THE INTERNATIONAL AIDS SOCIETY · 2022 Cite

Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission.

Journal Article Front Immunol · 2022 INTRODUCTION: Infants acquire maternal antibodies by Fc receptor transcytosis across the placenta during pregnancy. Fc receptors are expressed on immune cells and are important for activation of effector cell functions. METHODS: In this study, we evaluated ... Full text Link to item Cite

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

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

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

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

Incorporating the Cluster A and V1V2 Targets into a Minimal Structural Unit of the HIV-1 Envelope to Elicit a Cross-Clade Response with Potent Fc-Effector Functions.

Journal Article Vaccines (Basel) · August 31, 2021 The generation of a potent vaccine for the prevention and/or control of HIV-1 has been unsuccessful to date, despite decades of research. Existing evidence from both infected individuals and clinical trials support a role for non-neutralizing or weakly neu ... 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

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

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

A Cytometrist's Guide to Coordinating and Performing Effective COVID-19 Research.

Journal Article Cytometry A · January 2021 Cytometry is playing a crucial role in addressing the COVID-19 pandemic. In this commentary-written by a variety of stakeholders in the cytometry, immunology, and infectious disease communities-we review cytometry's role in the COVID-19 response and discus ... 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

Elimination of SHIV Infected Cells by Combinations of Bispecific HIVxCD3 DART® Molecules.

Journal Article Front Immunol · 2021 Bispecific HIVxCD3 DART molecules that co-engage the viral envelope glycoprotein (Env) on HIV-1-infected cells and the CD3 receptor on CD3+ T cells are designed to mediate the cytolysis of HIV-1-infected, Env-expressing cells. Using a novel ex vivo system ... Full text Link to item Cite

FlowKit: A Python Toolkit for Integrated Manual and Automated Cytometry Analysis Workflows.

Journal Article Front Immunol · 2021 An important challenge for primary or secondary analysis of cytometry data is how to facilitate productive collaboration between domain and quantitative experts. Domain experts in cytometry laboratories and core facilities increasingly recognize the need f ... Full text Open Access 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

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

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

Frequent Anti-V1V2 Responses Induced by HIV-DNA Followed by HIV-MVA with or without CN54rgp140/GLA-AF in Healthy African Volunteers.

Conference Microorganisms · November 4, 2020 Antibody responses that correlated with reduced risk of HIV acquisition in the RV144 efficacy trial were assessed in healthy African volunteers who had been primed three times with HIV-DNA (subtype A, B, C) and then randomized into two groups; group 1 was ... Full text Link to item Cite

Efficacy, pharmacokinetics and neurocognitive performance of dual, NRTI-sparing antiretroviral therapy in acute HIV-infection.

Journal Article AIDS · November 1, 2020 OBJECTIVES: The aim of this study was to evaluate penetration of antiretrovirals into compartments and efficacy of a dual, NRTI-sparing regimen in acute HIV infection (AHI). DESIGN: Single-arm, open-label pilot study of participants with AHI initiating rit ... Full text Link to item Cite

SMAC Mimetic Plus Triple-Combination Bispecific HIVxCD3 Retargeting Molecules in SHIV.C.CH505-Infected, Antiretroviral Therapy-Suppressed Rhesus Macaques.

Conference J Virol · October 14, 2020 The "shock-and-kill" human immunodeficiency virus type 1 (HIV-1) cure strategy involves latency reversal followed by immune-mediated clearance of infected cells. We have previously shown that activation of the noncanonical NF-κB pathway using an inhibitor ... Full text Link to item Cite

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

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

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

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

Engineering antibody-based molecules for HIV treatment and cure.

Journal Article Curr Opin HIV AIDS · September 2020 PURPOSE OF REVIEW: Immunotherapy strategies alternative to current antiretroviral therapies will need to address viral diversity while increasing the immune system's ability to efficiently target the latent virus reservoir. Antibody-based molecules can be ... 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

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

Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial.

Journal Article mBio · June 30, 2020 Antibodies (Abs) specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (C1/C2) were induced in the RV144 vaccine trial, where antibody-dependent cellular cytotoxicity (ADCC) correlated with reduced risk of HIV-1 infection. We comb ... Full text Link to item Cite

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

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

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

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

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

Curing HIV: Seeking to Target and Clear Persistent Infection.

Journal Article Cell · April 2, 2020 Human immunodeficiency virus type 1 (HIV-1) infection persists despite years of antiretroviral therapy (ART). To remove the stigma and burden of chronic infection, approaches to eradicate or cure HIV infection are desired. Attempts to augment ART with ther ... Full text Link to item Cite

HIV Env-Specific IgG Antibodies Induced by Vaccination of Neonatal Rhesus Macaques Persist and Can Be Augmented by a Late Booster Immunization in Infancy.

Journal Article mSphere · March 25, 2020 The HIV epidemics in infants and adolescent women are linked. Young women of childbearing age are at high risk for HIV infection and, due to poor HIV testing rates and low adherence to antiretroviral therapy, are at high risk for mother-to-infant transmiss ... 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

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

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

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

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

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

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

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

Redirection of Cord Blood T Cells and Natural Killer Cells for Elimination of Autologous HIV-1-Infected Target Cells Using Bispecific DART® Molecules.

Journal Article Front Immunol · 2020 Mother-to-child transmission of HIV-1 remains a major global health challenge. Currently, HIV-1-infected infants require strict lifelong adherence to antiretroviral therapy to prevent replication of virus from reservoirs of infected cells, and to halt prog ... Full text Open Access Link to item Cite

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

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

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

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

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

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

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

Oral Coadministration of an Intramuscular DNA/Modified Vaccinia Ankara Vaccine for Simian Immunodeficiency Virus Is Associated with Better Control of Infection in Orally Exposed Infant Macaques.

Journal Article AIDS Res Hum Retroviruses · March 2019 The majority of human immunodeficiency virus (HIV) type 1 infections in infants are acquired orally through breastfeeding. Toward development of a pediatric HIV vaccine to prevent breastmilk transmission, we tested the efficacy of a simultaneous oral and i ... Full text Link to item Cite

Coadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques.

Journal Article J Virol · March 1, 2019 Prevention of mother-to-child transmission (MTCT) is an indispensable component in combatting the global AIDS epidemic. A combination of passive broadly neutralizing antibody (bnAb) infusion and active vaccination promises to provide protection of infants ... Full text Link to item Cite

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

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

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

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

Knowns and Unknowns of Assaying Antibody-Dependent Cell-Mediated Cytotoxicity Against HIV-1.

Journal Article Front Immunol · 2019 It is now well-accepted that Fc-mediated effector functions, including antibody-dependent cellular cytotoxicity (ADCC), can contribute to vaccine-elicited protection as well as post-infection control of HIV viremia. This picture was derived using a wide ar ... Full text Link to item Cite

Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections.

Journal Article Front Immunol · 2019 Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution o ... 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 Front Immunol · 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 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

V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.

Journal Article Cell Rep · December 11, 2018 Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high- ... Full text Link to item Cite

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

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

Adjuvant-Dependent Enhancement of HIV Env-Specific Antibody Responses in Infant Rhesus Macaques.

Journal Article J Virol · October 15, 2018 Toward the goal of developing an effective HIV vaccine that can be administered in infancy to protect against postnatal and lifelong sexual HIV transmission risks, the current pilot study was designed to compare the effect of novel adjuvants on the inducti ... 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

Single-Cell Analysis of Quiescent HIV Infection Reveals Host Transcriptional Profiles that Regulate Proviral Latency.

Journal Article Cell Rep · October 2, 2018 A detailed understanding of the mechanisms that establish or maintain the latent reservoir of HIV will guide approaches to eliminate persistent infection. We used a cell line and primary cell models of HIV latency to investigate viral RNA (vRNA) expression ... Full text Link to item Cite

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

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

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

Markers of Tissue Repair and Cellular Aging Are Increased in the Liver Tissue of Patients With HIV Infection Regardless of Presence of HCV Coinfection.

Journal Article Open Forum Infect Dis · July 2018 Liver disease is a leading cause of HIV-related mortality. Hepatitis C virus (HCV)-related fibrogenesis is accelerated in the setting of HIV coinfection, yet the mechanisms underlying this aggressive pathogenesis are unclear. We identified formalin-fixed p ... Full text Open Access Link to item Cite

Interleukin-15-Stimulated Natural Killer Cells Clear HIV-1-Infected Cells following Latency Reversal Ex Vivo.

Journal Article J Virol · June 15, 2018 Current efforts toward human immunodeficiency virus (HIV) eradication include approaches to augment immune recognition and elimination of persistently infected cells following latency reversal. Natural killer (NK) cells, the main effectors of the innate im ... Full text Link to item Cite

Tandem bispecific broadly neutralizing antibody - a novel approach to HIV-1 treatment.

Journal Article J Clin Invest · June 1, 2018 The last decade has led to a significant advance in our knowledge of HIV-1 latency and immunity. However, we are still not close to finding a cure for HIV-1. Although combination antiretroviral therapy (cART) has led to increased survival, almost close to ... 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-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

A-102 Antibody binding to HIV-1 infected cells as mechanism for treatment of HIV infection

Conference JAIDS Journal of Acquired Immune Deficiency Syndromes · April 2018 Anti-HIV antibody function is not limited to capturing free virus but also includes the recognition of HIV-1 infected cells. Both neutralizing and nonneutralizing antibody responses recognizing HIV-1 envelope epitopes expressed on the cellular memb ... Full text 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

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

Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial.

Journal Article AIDS Res Hum Retroviruses · February 2018 We assessed the safety and immunogenicity of HIV-DNA priming using Zetajet™, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 μg (n = 10 ... Full text Link to item Cite

Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.

Journal Article mSphere · 2018 Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is o ... Full text Open Access 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

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

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

A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies.

Journal Article Retrovirology · October 10, 2017 BACKGROUND: Mutations rapidly accumulate in the HIV-1 genome after infection. Some of those mutations are selected by host immune responses and often cause viral fitness losses. This study is to investigate whether strongly selected mutations that are not ... Full text Link to item Cite

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

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

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

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

Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques.

Journal Article Clin Vaccine Immunol · October 2017 Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infa ... Full text Link to item Cite

Beyond Viral Neutralization.

Journal Article AIDS Res Hum Retroviruses · August 2017 It has been known for more than 30 years that HIV-1 infection drives a very potent B cell response resulting in the production of anti-HIV-1 antibodies targeting several viral proteins, particularly its envelope glycoproteins (Env). Env epitopes are expose ... Full text Link to item Cite

Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.

Journal Article AIDS Res Hum Retroviruses · August 2017 We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-M ... 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

HIV antibodies for treatment of HIV infection.

Journal Article Immunol Rev · January 2017 The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is ... Full text Link to item Cite

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Journal Article Current HIV Research · January 1, 2017 Full text Cite

Ending AIDS as a public health threat by 2030: Scientific Developments from the 2016 INTEREST Conference in Yaoundé, Cameroon.

Journal Article Antivir Ther · 2017 The underpinning theme of the 2016 INTEREST Conference held in Yaoundé, Cameroon, 3-6 May 2016 was ending AIDS as a public health threat by 2030. Focused primarily on HIV treatment, pathogenesis and prevention research in resource-limited settings, the con ... 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

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

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

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

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

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

Fixed-dose combination emtricitabine/tenofovir/efavirenz initiated during acute HIV infection; 96-week efficacy and durability.

Journal Article AIDS · November 28, 2016 BACKGROUND: Updated guidelines recommend immediate antiretroviral treatment (ART) during acute HIV infection (AHI), but efficacy data on regimens during AHI are limited. METHODS: We provide final data on a prospective, single-arm 96-week open-label study o ... Full text Link to item Cite

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

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

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

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

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

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

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

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

Envelope-specific B-cell populations in African green monkeys chronically infected with simian immunodeficiency virus.

Journal Article Nat Commun · July 6, 2016 African green monkeys (AGMs) are natural primate hosts of simian immunodeficiency virus (SIV). Interestingly, features of the envelope-specific antibody responses in SIV-infected AGMs are distinct from that of HIV-infected humans and SIV-infected rhesus mo ... 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

Variability of the IFN-γ ELISpot assay in the context of proficiency testing and bridging studies.

Journal Article J Immunol Methods · June 2016 Assays that assess cellular mediated immune responses performed under Good Clinical Laboratory Practice (GCLP) guidelines are required to provide specific and reproducible results. Defined validation procedures are required to establish the Standard Operat ... Full text Open Access 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

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

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

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

A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies.

Journal Article J Virol · February 15, 2016 Previous studies have shown that sera from HIV-1-infected individuals contain antibodies able to mediate antibody-dependent cellular cytotoxicity (ADCC). These antibodies preferentially recognize envelope glycoprotein (Env) epitopes induced upon CD4 bindin ... 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

Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial.

Journal Article PLoS One · 2016 BACKGROUND: A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant ... 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

Gnidimacrin, a Potent Anti-HIV Diterpene, Can Eliminate Latent HIV-1 Ex Vivo by Activation of Protein Kinase C β.

Journal Article J Med Chem · November 12, 2015 HIV-1-latency-reversing agents, such as histone deacetylase inhibitors (HDACIs), were ineffective in reducing latent HIV-1 reservoirs ex vivo using CD4 cells from patients as a model. This deficiency poses a challenge to current pharmacological approaches ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

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

Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.

Journal Article PLoS One · 2015 UNLABELLED: Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified ... Full text Open Access Link to item Cite

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

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

Aggregate complexes of HIV-1 induced by multimeric antibodies

Journal Article Retrovirology · December 2014 Full text Cite

Aggregate complexes of HIV-1 induced by multimeric antibodies.

Journal Article Retrovirology · October 2, 2014 BACKGROUND: Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible muco ... Full text Open Access Link to item Cite

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 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 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

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 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

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

Journal Article J Virol · July 2014 The RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated vaccine efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site of immune pressure in the HIV-1 envelope (Env) variable region 2 (V2) focused on residue 169, which ... Full text Link to item Cite

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

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

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

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

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

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

Journal Article Nature · January 23, 2014 A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that ... Full text Open Access Link to item Cite

The human antibody response to the surface of Mycobacterium tuberculosis.

Journal Article PLoS One · 2014 BACKGROUND: Vaccine-induced human antibodies to surface components of Haemophilus influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal antibodies to surface components of Mycobacterium tuberculosis are also protective in animal ... Full text Open Access Link to item Cite

Heterogeneity of Anti-V2 ADCC Ab Responses and Implications for Vaccine Development

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · November 1, 2013 Link to item Cite

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

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

Epitope specificity of human immunodeficiency virus-1 antibody dependent cellular cytotoxicity [ADCC] responses.

Journal Article Curr HIV Res · July 2013 Antibody dependent cellular cytotoxicity [ADCC] has been suggested to play an important role in control of Human Immunodeficiency Virus-1 [HIV-1] viral load and protection from infection. ADCC antibody responses have been mapped to multiple linear and conf ... Full text Link to item Cite

Mucosal immunization of lactating female rhesus monkeys with a transmitted/founder HIV-1 envelope induces strong Env-specific IgA antibody responses in breast milk.

Journal Article J Virol · June 2013 We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody respon ... Full text Link to item Cite

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

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

Protection afforded by an HIV vaccine candidate in macaques depends on the dose of SIVmac251 at challenge exposure.

Journal Article J Virol · March 2013 We used the simian immunodeficiency virus mac251 (SIV(mac251)) macaque model to study the effect of the dose of mucosal exposure on vaccine efficacy. We immunized macaques with a DNA prime followed by SIV gp120 protein immunization with ALVAC-SIV and gp120 ... Full text Link to item Cite

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

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

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

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

Acute HIV-1 infection in the Southeastern United States: a cohort study.

Journal Article AIDS Res Hum Retroviruses · January 2013 In 1998 a collaboration between Duke University and the University of North Carolina, Chapel Hill (UNC) was founded to enhance identification of persons with acute HIV-1 infection (AHI). The Duke-UNC AHI Research Consortium Cohort consists of patients ≥18 ... Full text Link to item Cite

Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.

Journal Article J Clin Invest · January 2013 HIV-1 accumulates mutations in and around reactive epitopes to escape recognition and killing by CD8+ T cells. Measurements of HIV-1 time to escape should therefore provide information on which parameters are most important for T cell-mediated in vivo cont ... Full text Link to item Cite

Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV.

Journal Article PLoS One · 2013 Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test th ... Full text Link to item Cite

High antibody-dependent cellular cytotoxicity responses are correlated with strong CD8 T cell viral suppressive activity but not with B57 status in HIV-1 elite controllers.

Journal Article PLoS One · 2013 The role of Antibody-dependent cellular cytotoxicity (ADCC) responses in HIV-1 controllers is still unclear due to the heterogeneity of these patients. We analyzed 67 HIV-1 controllers and found significantly higher levels of ADCC antibodies in controllers ... 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

Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines.

Journal Article Nat Med · November 2012 Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of ... Full text Link to item Cite

Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome.

Journal Article Retrovirology · October 30, 2012 BACKGROUND: A modest change in HIV-1 fitness can have a significant impact on viral quasispecies evolution and viral pathogenesis, transmission and disease progression. To determine the impact of immune escape mutations selected by cytotoxic T lymphocytes ... Full text Link to item Cite

Massive CD8 T cell response to primary HIV infection in the setting of severe clinical presentation.

Journal Article AIDS Res Hum Retroviruses · August 2012 Acute HIV-1 infection causes a rapid total body depletion of CD4(+) T cells in most individuals and HIV-1-specific CD8(+) T cell expansion in response to viral replication. A numerically high CD8 T cell response may indicate limited T cell repertoire again ... 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

Distinct kinetics of Gag-specific CD4+ and CD8+ T cell responses during acute HIV-1 infection.

Journal Article J Immunol · March 1, 2012 HIV infection is characterized by a gradual deterioration of immune function, mainly in the CD4 compartment. To better understand the dynamics of HIV-specific T cells, we analyzed the kinetics and polyfunctional profiles of Gag-specific CD4(+) and CD8(+) T ... Full text Link to item Cite

Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge.

Journal Article Vaccine · February 27, 2012 The current study assessed the immunogenicity and protective efficacy of various prime-boost vaccine regimens in rhesus macaques using combinations of recombinant DNA (rDNA), recombinant MVA (rMVA), and subunit gp140 protein. The rDNA and rMVA vectors were ... Full text Link to item Cite

SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses.

Journal Article Vaccine · February 21, 2012 BACKGROUND: Vaccine regimens using different agents for priming and boosting have become popular for enhancing T cell and Ab responses elicited by candidate HIV/AIDS vaccines. Here we use a simian model to evaluate immunogenicity and protective efficacy of ... Full text Link to item Cite

Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys.

Journal Article Nature · January 4, 2012 Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitiv ... 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

Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection.

Journal Article J Virol · October 2011 HIV-1 often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. We used single-genome amplification and sequencing of complete HIV genomes to identify longitudinal changes in the transmitted/founder virus from th ... 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

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 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

Prevention of infection by a granulocyte-macrophage colony-stimulating factor co-expressing DNA/modified vaccinia Ankara simian immunodeficiency virus vaccine.

Journal Article J Infect Dis · July 1, 2011 A simian immunodeficiency virus (SIV) vaccine coexpressing granulocyte-macrophage colony stimulating factor (GM-CSF) prevented infection in 71% of macaques that received 12 rectal challenges. The SIVsmE660 challenge had the tropism of incident human immuno ... Full text Link to item Cite

Cross-sectional detection of acute HIV infection: timing of transmission, inflammation and antiretroviral therapy.

Journal Article PLoS One · May 10, 2011 BACKGROUND: Acute HIV infection (AHI) is a critical phase of infection when irreparable damage to the immune system occurs and subjects are very infectious. We studied subjects with AHI prospectively to develop better treatment and public health interventi ... Full text Link to item Cite

Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection.

Journal Article Blood · May 5, 2011 A highly complex network of coinhibitory and costimulatory receptors regulates the outcome of virus-specific CD8(+) T-cell responses. Here, we report on the expression patterns of multiple inhibitory receptors on HIV-specific, cytomegalovirus-specific, and ... Full text Link to item Cite

Discriminating between latent and active tuberculosis with multiple biomarker responses.

Journal Article Tuberculosis (Edinb) · May 2011 We sought to identify biomarker responses to tuberculosis specific antigens which could 1) improve the diagnosis of tuberculosis infection and 2) allow the differentiation of active and latent infections. Seventy subjects with active tuberculosis (N = 12), ... Full text Link to item Cite

Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection.

Journal Article AIDS · April 24, 2011 OBJECTIVE: Characterize responses to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment (ART) initiated during acute HIV infection (AHI). DESIGN: This was a prospective, single-arm evaluation of once-daily, co-formulated ... 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 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

Optimization of storage and shipment of cryopreserved peripheral blood mononuclear cells from HIV-infected and uninfected individuals for ELISPOT assays.

Journal Article J Immunol Methods · December 15, 2010 Functional immunologic assays using cryopreserved peripheral blood mononuclear cells (PBMC) are influenced by blood processing, storage and shipment. The objective of this study was to compare the viability, recovery and ELISPOT results of PBMC stored and ... Full text Link to item Cite

Vaccine-Elicited IgG Subclasses and Functional Antibodies

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2010 Link to item Cite

Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.

Journal Article PLoS One · August 10, 2010 BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). M ... Full text Open Access Link to item Cite

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

Loss of DNAM-1 contributes to CD8+ T-cell exhaustion in chronic HIV-1 infection.

Journal Article Eur J Immunol · April 2010 The hallmark of chronic viral infections is a progressive exhaustion of antigen-specific CD8(+) T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory recepto ... Full text Link to item Cite

Performance of serum-supplemented and serum-free media in IFNgamma Elispot Assays for human T cells.

Journal Article Cancer Immunol Immunother · April 2010 The choice of serum for supplementation of media for T cell assays and in particular, Elispot has been a major challenge for assay performance, standardization, optimization, and reproducibility. The Assay Working Group of the Cancer Vaccine Consortium (CV ... Full text Link to item Cite

Perforin and IL-2 upregulation define qualitative differences among highly functional virus-specific human CD8 T cells.

Journal Article PLoS Pathog · March 5, 2010 The prevailing paradigm of T lymphocyte control of viral replication is that the protective capacity of virus-specific CD8(+) T cells is directly proportional to the number of functions they can perform, with IL-2 production capacity considered critical. H ... Full text Open Access Link to item Cite

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection.

Journal Article J Exp Med · June 8, 2009 Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1-specific T cell response induced i ... 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

HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC.

Journal Article PLoS Pathog · May 2009 The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple ear ... Full text Link to item Cite

Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial.

Journal Article Vaccine · January 7, 2009 There is an urgent need for a vaccine capable of preventing HIV infection or the development of HIV-related disease. A number of approaches designed to stimulate HIV-specific CD8+ cytotoxic T cell responses together with helper responses are presently unde ... Full text Link to item Cite

T Cell Escape in Subjects with Acute HIV-1 Infection

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2008 Link to item Cite

Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design.

Journal Article J Virol · August 2008 The death of CD4(+) CCR5(+) T cells is a hallmark of human immunodeficiency virus (HIV) infection. We studied the plasma levels of cell death mediators and products--tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas ligand, TNF rec ... Full text Link to item Cite

Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial.

Journal Article Diabetes Care · May 2008 OBJECTIVE: Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) are risk factors for diabetes, cardiovascular disease (CVD), and kidney disease. We determined the effects of ramipril and rosiglitazone on combined and individual CVD and re ... Full text Link to item Cite

Endpoint Assays in HIV-1 Vaccine Trials: Functioning in a Good Laboratory Practices Environment

Chapter · April 8, 2008 An HIV-1 vaccine is the best public health tool for stemming the AIDS pandemic, now in its third decade. Studies from HIV-1 infected humans who control infection, animal model experiments, as well as historic experience with licensed vaccines suggest that ... Full text Cite

Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)-uninfected adults.

Journal Article Vaccine · January 10, 2008 We evaluated EP HIV-1090 vaccine, a DNA plasmid encoding 21 cytotoxic T-lymphocyte (CTL) epitopes of human immunodeficiency virus type 1 (HIV-1) and the pan-DR helper T-lymphocyte epitope (PADRE), in a dose escalation, randomized, double-blinded, placebo-c ... Full text Link to item Cite

Neutralizing and other antiviral antibodies in HIV-1 infection and vaccination.

Journal Article Curr Opin HIV AIDS · May 2007 PURPOSE OF REVIEW: New findings continue to support the notion that broadly crossreactive neutralizing antibody induction is a worthwhile and achievable goal for HIV-1 vaccines. Immunogens are needed that can overcome the genetic variability and complex im ... Full text Link to item Cite

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

Effect of ramipril on the incidence of diabetes.

Journal Article N Engl J Med · October 12, 2006 BACKGROUND: Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension. METHODS: In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we r ... Full text Link to item Cite

Antigen-specific T-cell-mediated immunity after HIV-1 infection: implications for vaccine control of HIV development.

Journal Article Expert Rev Vaccines · August 2006 The definition of immune correlates of protection in HIV-1 infection is pivotal to the design of successful vaccine candidates and strategies. Although significant methodological and conceptual strides have been made in our understanding of HIV-specific ce ... Full text Link to item Cite

Excellent safety and tolerability of the human immunodeficiency virus type 1 pGA2/JS2 plasmid DNA priming vector vaccine in HIV type 1 uninfected adults.

Journal Article AIDS Res Hum Retroviruses · July 2006 A vaccine consisting of DNA priming followed by recombinant modified vaccinia Ankara (rMVA) boosting has achieved long-term control of a pathogenic challenge with a chimera of simian and human immunodeficiency viruses (SHIV-89.6P) in rhesus macaques. Based ... Full text Link to item Cite

Measurement of cytokine release at the single cell level using the ELISPOT assay.

Journal Article Methods · April 2006 The enzyme-linked immunospot (ELISPOT) assay took its design concept from traditional ELISA techniques and evolved over the years from a method for detecting antibodies secreted from B cells to a method for detecting cytokines or other soluble mediators se ... 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

Naïve T cells are maintained in the periphery during the first 3 months of acute HIV-1 infection: implications for analysis of thymus function.

Journal Article J Clin Immunol · September 2005 A key determinant of T cell dynamics in HIV-1 infection is the status of thymic function. To date, most studies of the impact of HIV-1 on the thymus during early HIV-1 infection have been done in samples collected in the interval of 3-12 months after infec ... 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

Immunodominance and cross-reactivity of B5703-restricted CD8 T lymphocytes from HIV type 1 subtype C-infected Ethiopians.

Journal Article AIDS Res Hum Retroviruses · March 2005 The HLA-B57 allele family is associated with slow progression to disease in HIV-1-infected individuals and restricts a potent CD8 response against the p24 protein. This study was designed to assess the sequence variation and the CD8 response against B57-re ... 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

Standardization and validation issues of the ELISPOT assay.

Journal Article Methods Mol Biol · 2005 During the last 20 yr, the enzyme-linked immunospot (ELISPOT) assay has emerged as one of the most important and widely used assays to monitor immune responses in humans and a variety of other species. With the ELISPOT assay, immune cell frequencies can be ... Full text Link to item Cite

Results of an ELISPOT proficiency panel conducted in 11 laboratories participating in international human immunodeficiency virus type 1 vaccine trials.

Journal Article AIDS Res Hum Retroviruses · January 2005 We used an external quality assurance (EQA) panel to assess laboratory competency and comparability when performing ELISPOT assays in support of human immunodeficiency virus type 1 (HIV-1) vaccine trials. Cell recovery, viability, and frequency of interfer ... Full text Link to item Cite

Absence of immunodominant anti-Gag p17 (SL9) responses among Gag CTL-positive, HIV-uninfected vaccine recipients expressing the HLA-A*0201 allele.

Journal Article J Immunol · August 1, 2004 According to a number of previous reports, control of HIV replication in humans appears to be linked to the presence of anti-HIV-1 Gag-specific CD8 responses. During the chronic phase of HIV-1 infection, up to 75% of the HIV-infected individuals who expres ... Full text Link to item Cite

HLA-A and -B allele expression and ability to develop anti-Gag cross-clade responses in subtype C HIV-1-infected Ethiopians.

Journal Article Hum Immunol · June 2004 A cohort of 35 human immunodeficiency virus type 1 (HIV-1) subtype C-infected Ethiopians was studied to define the HLA phenotype in all 35 subjects and highly conserved Gag protein regions involved in cross-clade cell-mediated immunity. Full-length Gag vir ... Full text Link to item Cite

Automating Procedures for Processing, Cryopreservation, Storage, and Manipulation of Human Peripheral Blood Mononuclear Cells

Journal Article Journal of Laboratory Automation · January 1, 2004 Cell-mediated immune responses have been found to play a crucial role in the protection from, or amelioration of, many human diseases. There are many vaccine trials being conducted where the most important immune assessment consists of measuring T cell res ... Full text Cite

A cluster of HIV type 1 subtype C sequences from Ethiopia, observed in full genome analysis, is not sustained in subgenomic regions.

Journal Article AIDS Res Hum Retroviruses · December 2003 The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. One approach to minimize genetic diversity in the evaluation of HIV-1 vaccines is to match the vaccine sequence to the predominant subtype in a vaccine cohort. Over two million Ethio ... 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

A panel of MHC class I restricted viral peptides for use as a quality control for vaccine trial ELISPOT assays.

Journal Article J Immunol Methods · February 1, 2002 Vaccines in general and HIV vaccines in particular are focusing ever more on the induction of cellular immunity specifically the generation of cytotoxic T cells (CTL). As progress is made towards developing a safe and effective HIV vaccine, there is a need ... Full text Link to item Cite

CD8 CTL responses in vaccines: emerging patterns of HLA restriction and epitope recognition.

Journal Article Immunol Lett · November 1, 2001 We evaluated MHC-class I-restricted CTL responses induced by HIV-1 clade B-based vaccines in nine HIV-1 seronegative vaccine recipients with regard to their patterns of HLA restriction and epitope recognition. We found that seven of nine volunteers develop ... Full text Link to item Cite

Near full-length clones and reference sequences for subtype C isolates of HIV type 1 from three different continents.

Other AIDS Res Hum Retroviruses · January 20, 2001 Among the major circulating HIV-1 subtypes, subtype C is the most prevalent. To generate full-length subtype C clones and sequences, we selected 13 primary (PBMC-derived) isolates from Zambia, India, Tanzania, South Africa, Brazil, and China, which were id ... Full text Link to item Cite

Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines.

Journal Article AIDS Res Hum Retroviruses · September 20, 2000 One of the fundamental goals of current strategies to develop an efficacious vaccine for AIDS is the elicitation of cytotoxic T lymphocyte (CTL) reactivities capable of recognizing cells infected with different subtypes of the human immunodeficiency virus ... 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

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

Journal Article AIDS Res Hum Retroviruses · March 20, 2000 The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200- ... Full text Link to item Cite

Recombinant Bacillus Calmette-Guerin as a Potential Vector for Preventive HIV Type 1 Vaccines

Journal Article AIDS Research and Human Retroviruses · January 20, 2000 Full text Cite

Lack of infection in HIV-exposed individuals is associated with a strong CD8(+) cell noncytotoxic anti-HIV response.

Journal Article Proc Natl Acad Sci U S A · February 2, 1999 Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, f ... Full text Link to item Cite

The CD8+ cell non-cytotoxic, anti-HIV response is associated with protection in HIV-exposed, uninfected individuals

Conference FASEB Journal · 1998 Several multiply HIV-exposed, uninfected cohorts were studied for evidence of correlates of protective immunity. This uninfected high risk population was comprised of the IV drug-sharing and/or sexual partners of infected individuals. Genotyping of cells f ... Cite

Cellular immune responses to candidate AIDS vaccines

Conference 11E COLLOQUE DES CENT GARDES · January 1, 1998 Link to item Cite

Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy.

Journal Article Blood · September 15, 1997 In the attempt to develop immunotherapeutic strategies for acquired immunodeficiency syndrome capable of activating effector cells in an antigen-specific manner while maintaining the broadest possible T-cell repertoire, we evaluated two canarypox (ALVAC)-b ... Link to item Cite

Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers.

Journal Article Proc Natl Acad Sci U S A · February 18, 1997 A fundamental goal of current strategies to develop an efficacious vaccine for AIDS is the elicitation of broadly reactive cytotoxic T lymphocyte (CTL) reactivities capable of destroying virally infected targets. Recent application of recombinant canarypox ... Full text Link to item Cite

Oligoclonal CD8 lymphocytes from persons with asymptomatic human immunodeficiency virus (HIV) type 1 infection inhibit HIV-1 replication.

Journal Article J Infect Dis · October 1995 CD8 lymphocytes from asymptomatic human immunodeficiency virus (HIV) type 1-infected patients can suppress virus production from infected CD4 cells. Suppressive activity is separate and distinct from cytotoxic T lymphocyte (CTL) reactivities and is likely ... Full text Link to item Cite

IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp).

Journal Article Clin Exp Immunol · August 1995 CD8+ cytotoxic T lymphocytes are an important component in the immunologic control of human viral diseases. IL-7, a stromal cell-derived cytokine, has been demonstrated to enhance both anti-tumour and anti-viral CTL as well as lymphokine-activated killer ( ... Full text Link to item Cite

Comparison of anti-HIV-1 ADCC reactivities in infected humans and chimpanzees.

Journal Article J Acquir Immune Defic Syndr (1988) · April 1994 Despite its shortcomings as a disease model, the chimpanzee is still the most relevant animal model for human immunodeficiency virus type 1 (HIV-1) infection. Previous studies have revealed qualitative differences between human and chimpanzee anti-HIV-1 re ... Link to item Cite

The impact of HIV-1 infection on phenotypic and functional parameters of cellular immunity in chimpanzees.

Journal Article AIDS Res Hum Retroviruses · July 1993 As a means of assessing the immunological impact of HIV infection in the chimpanzee, as well as the participation of the cellular components in the control of HIV infection in these animals, various aspects of cellular immunity were investigated in chronic ... Full text Link to item Cite

In vivo genetic variability of the human immunodeficiency virus type 2 V3 region.

Journal Article J Virol · July 1992 The principal neutralizing epitope of the human immunodeficiency virus type 1 (HIV-1) lies between two invariant cysteines in the third variable region (V3) of the viral envelope (gp120), and its amino acid sequence varies among different HIV-1 isolates. H ... Full text Link to item Cite

HTLV REACTIVITY IN NORMAL POPULATION OF SOUTHERN APULIA (ITALY)

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · January 1, 1990 Link to item Cite

ANTIBODY PREVALENCE TO TORCH AGENTS IN PREGNANT-WOMEN AND RELATIVE RISK OF CONGENITAL INFECTIONS IN ITALY (LIGURIA)

Journal Article BIOLOGICAL RESEARCH IN PREGNANCY AND PERINATOLOGY · January 1, 1987 Link to item Cite

Antibody prevalence to torch agents in pregnant women and relative risk of congenital infections in Italy (Liguria).

Journal Article Biol Res Pregnancy Perinatol · 1987 A study on the prevalence of seropositivity to T.gondii, Rubella virus, Cytomegalovirus and Herpes simplex virus (type 1 and type 2) was carried out in pregnant women aged 15-45 years. An overall prevalence of 40.7% to T.gondii, of 90.1% to Rubella virus, ... Link to item Cite