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Kevin O'Neil Saunders

Kevin O'Neil Saunders

Professor in Surgery
Surgery, Surgical Sciences
kevin.saunders@duke.edu
Box 3020 Med Ctr, Durham, NC 27710
2 Genome Court, 4074 Medical Science Research Building 2, Durham, NC 27710

Selected Publications

An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations.

Journal Article Sci Transl Med · January 8, 2025 Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Becaus ... Full text Link to item Cite

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

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

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Journal Article Nat Commun · November 3, 2024 Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for ... Full text Link to item Cite

Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.

Journal Article J Virol · September 17, 2024 Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unli ... Full text Link to item Cite

Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families.

Journal Article PLoS Pathog · September 2024 Broadly reactive antibodies that target sequence-diverse antigens are of interest for vaccine design and monoclonal antibody therapeutic development because they can protect against multiple strains of a virus and provide a barrier to evolution of escape m ... Full text Link to item Cite

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

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

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

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

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

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

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

Microsecond dynamics control the HIV-1 Envelope conformation.

Journal Article Sci Adv · February 2, 2024 The HIV-1 Envelope (Env) glycoprotein facilitates host cell fusion through a complex series of receptor-induced structural changes. Although remarkable progress has been made in understanding the structures of various Env conformations, microsecond timesca ... Full text Link to item Cite

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

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

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

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

Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates.

Journal Article bioRxiv · December 19, 2023 Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits ne ... Full text Link to item Cite

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

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

Guiding HIV-1 vaccine development with preclinical nonhuman primate research.

Journal Article Curr Opin HIV AIDS · November 1, 2023 PURPOSE OF THE REVIEW: Nonhuman primates (NHPs) are seen as the closest animal model to humans in terms of anatomy and immune system makeup. Here, we review how preclinical studies in this model system are teaching the field of HIV vaccinology the basic im ... Full text Link to item Cite

Progress with induction of HIV broadly neutralizing antibodies in the Duke Consortia for HIV/AIDS Vaccine Development.

Journal Article Curr Opin HIV AIDS · November 1, 2023 PURPOSE OF REVIEW: Design of an HIV vaccine that can induce broadly neutralizing antibodies (bnAbs) is a major goal. However, HIV bnAbs are not readily made by the immune system. Rather HIV bnAbs are disfavored by a number of virus and host factors. The pu ... Full text Link to item Cite

Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice.

Journal Article Cell Rep · October 31, 2023 The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vacc ... 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

Progress in vaccine development for infectious diseases-a Keystone Symposia report.

Journal Article Ann N Y Acad Sci · June 2023 The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the ... Full text Link to item Cite

Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage.

Journal Article Nat Commun · May 15, 2023 Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens ... Full text Link to item Cite

Identification of CDRH3 loops in the B cell receptor repertoire that can be engaged by candidate immunogens.

Journal Article PLoS Pathog · May 2023 A major goal for the development of vaccines against rapidly mutating viruses, such as influenza or HIV, is to elicit antibodies with broad neutralization capacity. However, B cell precursors capable of maturing into broadly neutralizing antibodies (bnAbs) ... Full text Link to item Cite

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

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

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

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

Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies.

Journal Article Nat Rev Immunol · March 2023 After nearly four decades of research, a safe and effective HIV-1 vaccine remains elusive. There are many reasons why the development of a potent and durable HIV-1 vaccine is challenging, including the extraordinary genetic diversity of HIV-1 and its compl ... Full text Link to item Cite

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

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

Structure-Based Stabilization of SOSIP Env Enhances Recombinant Ectodomain Durability and Yield.

Journal Article J Virol · January 31, 2023 The envelope glycoprotein (Env) is the main focus of human immunodeficiency virus type 1 (HIV-1) vaccine development due to its critical role in viral entry. Despite advances in protein engineering, many Env proteins remain recalcitrant to recombinant expr ... Full text Link to item Cite

Human Immunodeficiency Virus Vaccines

Chapter · January 1, 2023 HIV-1 vaccine development is a critical global health priority. The reasons why we do not have an HIV-1 vaccine as yet are many, including a dense envelop glycan shield, rare neutralizing B cell precursors, the need for improbable neutralizing antibody mut ... Full text Cite

Nebulized mRNA-Encoded Antibodies Protect Hamsters from SARS-CoV-2 Infection.

Journal Article Adv Sci (Weinh) · December 2022 Despite the success of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines, there remains a clear need for new classes of preventatives for respiratory viral infections due to vaccine hesitancy, lack of sterilizing immunity, and for at-ri ... Full text Link to item Cite

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

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

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

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

Self-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation.

Journal Article Sci Adv · September 23, 2022 To develop vaccines for certain key global pathogens such as HIV, it is crucial to elicit both neutralizing and non-neutralizing Fc-mediated effector antibody functions. Clinical evidence indicates that non-neutralizing antibody functions including antibod ... Full text Link to item Cite

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

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

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

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

B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates.

Journal Article Cell Rep · June 28, 2022 HIV-1 envelope (Env) proteins designed to induce neutralizing antibody responses allow study of the role of affinities (equilibrium dissociation constant [KD]) and kinetic rates (association/dissociation rates) on B cell antigen recognition. It is unclear ... Full text Link to item Cite

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

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

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

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

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

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

Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial.

Journal Article Nat Med · May 2022 Adeno-associated viral vector-mediated transfer of DNA coding for broadly neutralizing anti-HIV antibodies (bnAbs) offers an alternative to attempting to induce protection by vaccination or by repeated infusions of bnAbs. In this study, we administered a r ... Full text Link to item Cite

Development of mRNA manufacturing for vaccines and therapeutics: mRNA platform requirements and development of a scalable production process to support early phase clinical trials.

Journal Article Transl Res · April 2022 The remarkable success of SARS CoV-2 mRNA-based vaccines and the ensuing interest in mRNA vaccines and therapeutics have highlighted the need for a scalable clinical-enabling manufacturing process to produce such products, and robust analytical methods to ... Full text Open Access 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

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

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

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

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

Strategies for induction of HIV-1 envelope-reactive broadly neutralizing antibodies.

Journal Article J Int AIDS Soc · November 2021 INTRODUCTION: A primary focus of HIV-1 vaccine development is the activation of B cell receptors for naïve or precursor broadly neutralizing antibodies (bnAbs), followed by expansion and maturation of bnAb B cell lineage intermediates leading to highly aff ... Full text Link to item Cite

Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice.

Journal Article Science · August 27, 2021 The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate ... Full text Link to item Cite

Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations.

Journal Article Cell Rep · August 17, 2021 Elicitation of broadly neutralizing antibodies (bnAbs) by an HIV vaccine will involve priming the immune system to activate antibody precursors, followed by boosting immunizations to select for antibodies with functional features required for neutralizatio ... Full text Link to item Cite

Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.

Journal Article Science · August 6, 2021 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant ... Full text Link to item Cite

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

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

HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth.

Journal Article Sci Rep · July 14, 2021 A major challenge in developing an effective vaccine against HIV-1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV-1 strains, protective antibodies must be able to bind and neutralize a widely mutate ... Full text Link to item Cite

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

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

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

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

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

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

Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells.

Journal Article Cell Rep · May 25, 2021 Understanding and eliciting protective immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent priority. To facilitate these objectives, we profile the repertoire of human leukocyte antigen class II (HLA-II)-bound pept ... Full text Open Access 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

Broad neutralization of H1 and H3 viruses by adjuvanted influenza HA stem vaccines in nonhuman primates.

Journal Article Sci Transl Med · March 3, 2021 Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most of the seasonal epidemics observed in humans and are the ... Full text Link to item Cite

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

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

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

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

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

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

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

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

Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.

Journal Article Science · January 8, 2021 Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency virus ... Full text Open Access 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

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

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

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

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

Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs.

Journal Article NPJ Vaccines · November 18, 2020 A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactiv ... Full text Link to item Cite

RAB11FIP5-Deficient Mice Exhibit Cytokine-Related Transcriptomic Signatures.

Journal Article Immunohorizons · November 10, 2020 Rab11 recycling endosomes are involved in immunological synaptic functions, but the roles of Rab11 family-interacting protein 5 (Rab11Fip5), one of the Rab11 effectors, in the immune system remain obscure. Our previous study demonstrated that RAB11FIP5 tra ... Full text Link to item Cite

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

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

A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice.

Journal Article Immunity · October 13, 2020 SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, ... Full text Link to item Cite

Exploiting Pre-Existing CD4+ T Cell Help from Bacille Calmette-Guérin Vaccination to Improve Antiviral Antibody Responses.

Journal Article J Immunol · July 15, 2020 The continuing emergence of viral pathogens and their rapid spread into heavily populated areas around the world underscore the urgency for development of highly effective vaccines to generate protective antiviral Ab responses. Many established and newly e ... Full text Link to item Cite

Pandemic Preparedness: Developing Vaccines and Therapeutic Antibodies For COVID-19.

Journal Article Cell · June 25, 2020 The SARS-CoV-2 pandemic that causes COVID-19 respiratory syndrome has caused global public health and economic crises, necessitating rapid development of vaccines and therapeutic countermeasures. The world-wide response to the COVID-19 pandemic has been un ... 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

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

Journal Article NPJ Vaccines · May 8, 2020 Despite incredible scientific efforts, there is no cure for HIV infection. While antiretroviral treatment (ART) can help control the virus and prevent transmission, it cannot eradicate HIV from viral reservoirs established before the initiation of therapy. ... Full text Link to item Cite

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

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

Immune checkpoint modulation enhances HIV-1 antibody induction.

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

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

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

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

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

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

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

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

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

Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements.

Journal Article Nat Commun · January 24, 2020 The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion element ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates.

Journal Article PLoS Biol · June 2019 Peptide immunogens provide an approach to focus antibody responses to specific neutralizing sites on the HIV envelope protein (Env) trimer or on other pathogens. However, the physical characteristics of peptide immunogens can limit their pharmacokinetic an ... Full text Link to item Cite

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

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

Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.

Journal Article Nat Commun · February 8, 2019 Somatic mutations within antibody variable and framework regions (FWR) can alter thermostability and structural flexibility, but their impact on functional potency is unclear. Here we study thermostability and use molecular dynamics (MD) simulations to ass ... Full text Link to item Cite

Author Correction: A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite.

Journal Article Nat Med · January 2019 In the version of this article originally published, data were incorrectly ascribed to monoclonal antibody CIS34 because of a labeling error. The data were generated with monoclonal antibody CIS04. Full details can be found in the correction notice. ... Full text Link to item Cite

Consistent elicitation of cross-clade HIV-neutralizing responses achieved in guinea pigs after fusion peptide priming by repetitive envelope trimer boosting.

Journal Article PLoS One · 2019 The vaccine elicitation of broadly neutralizing responses is a central goal of HIV research. Recently, we elicited cross-clade neutralizing responses against the N terminus of the fusion peptide (FP), a critical component of the HIV-entry machinery. While ... Full text Link to item Cite

Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life.

Journal Article Front Immunol · 2019 Antibodies and Fc-fusion antibody-like proteins have become successful biologics developed for cancer treatment, passive immunity against infection, addiction, and autoimmune diseases. In general these biopharmaceuticals can be used for blocking protein:pr ... Full text Link to item Cite

Antibody responses to the HIV-1 envelope high mannose patch.

Chapter · 2019 Neutralizing antibodies against human immunodeficiency virus subtype 1 (HIV-1) bind to its envelope glycoprotein (Env). Half of the molecular mass of Env is carbohydrate making it one of the most heavily glycosylated proteins known in nature. HIV-1 Env gly ... Full text Link to item Cite

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

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

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

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

Macaque SHIV Induction of 2G12-like Broadly Neutralizing Antibodies

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

Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.

Journal Article Cell Host Microbe · June 13, 2018 HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mu ... Full text Open Access Link to item Cite

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

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

Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape.

Journal Article J Virol · May 15, 2018 Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ∼35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern ... Full text Link to item Cite

A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite.

Journal Article Nat Med · May 2018 Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) cir ... Full text Link to item Cite

Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on the Middle East respiratory syndrome coronavirus spike glycoprotein to avoid neutralization escape

Journal Article Journal of Virology · May 1, 2018 Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ~35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern ... Full text Cite

Glycoengineering HIV-1 Env creates 'supercharged' and 'hybrid' glycans to increase neutralizing antibody potency, breadth and saturation.

Journal Article PLoS Pathog · May 2018 The extensive glycosylation of HIV-1 envelope (Env) glycoprotein leaves few glycan-free holes large enough to admit broadly neutralizing antibodies (bnAb). Consequently, most bnAbs must inevitably make some glycan contacts and avoid clashes with others. 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody Gene Transfer Protects Nonhuman Primates from Mucosal Simian-Human Immunodeficiency Virus Infection.

Journal Article J Virol · August 2015 Broadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, d ... Full text Link to item Cite

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

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

Sustained Delivery of a Broadly Neutralizing Antibody in Nonhuman Primates Confers Long-Term Protection against Simian/Human Immunodeficiency Virus Infection.

Journal Article J Virol · June 2015 UNLABELLED: Pathogen-specific neutralizing antibodies protect against many viral infections and can potentially prevent human immunodeficiency virus (HIV) transmission in humans. However, neutralizing antibodies have so far only been shown to protect nonhu ... Full text Link to item Cite

Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection.

Journal Article Cell · April 23, 2015 HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here, we characterize the rate of maturation and extent of diversity for the lineag ... Full text Link to item Cite

The Cellular and Molecular Biology of HIV-1 Broadly Neutralizing Antibodies

Chapter · January 1, 2015 Induction of neutralizing antibodies capable of protecting against human immunodeficiency virus 1 (HIV-1) infection is a key goal of HIV-1 vaccine development. The target of neutralizing antibodies is the HIV-1 envelope (Env) protein on the virion surface. ... Full text Cite

Enhanced neonatal Fc receptor function improves protection against primate SHIV infection.

Journal Article Nature · October 30, 2014 To protect against human immunodeficiency virus (HIV-1) infection, broadly neutralizing antibodies (bnAbs) must be active at the portals of viral entry in the gastrointestinal or cervicovaginal tracts. The localization and persistence of antibodies at thes ... Full text Link to item Cite

Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer.

Journal Article Neuro Oncol · October 2014 BACKGROUND: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, w ... Full text Link to item Cite

Antibodies VRC01 and 10E8 neutralize HIV-1 with high breadth and potency even with Ig-framework regions substantially reverted to germline.

Journal Article J Immunol · February 1, 2014 Abs capable of effectively neutralizing HIV-1 generally exhibit very high levels of somatic hypermutation, both in their CDR and framework-variable regions. In many cases, full reversion of the Ab-framework mutations back to germline results in substantial ... Full text Link to item Cite

The design and evaluation of HIV-1 vaccines.

Journal Article AIDS · June 19, 2012 There is renewed optimism that the goal of developing a highly effective AIDS vaccine is attainable. The HIV-1 vaccine field has seen its first trial of a vaccine candidate that prevents infection. Although modest in efficacy, this finding, along with the ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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