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Xiaoying Shen

Associate Professor in Surgery
Surgery, Surgical Sciences
Box 2926 DUMC, Durham, NC 27710
205 SORF, 915 S. LaSalle Street, Box 2926, Duke University Medical Center, Durham, NC 27710

Selected Publications


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Journal Article bioRxiv · June 16, 2023 During the SARS-CoV-2 pandemic, multiple variants escaping pre-existing immunity emerged, causing concerns about continued protection. Here, we use antigenic cartography to analyze patterns of cross-reactivity among a panel of 21 variants and 15 groups of ... Full text Open Access 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

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

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

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

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

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

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

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

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

Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1.

Journal Article Front Immunol · 2023 INTRODUCTION: Neutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an ardu ... Full text Link to item Cite

Corrigendum: Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1.

Journal Article Front Immunol · 2023 [This corrects the article DOI: 10.3389/fimmu.2023.1271686.]. ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Journal Article bioRxiv · June 16, 2023 During the SARS-CoV-2 pandemic, multiple variants escaping pre-existing immunity emerged, causing concerns about continued protection. Here, we use antigenic cartography to analyze patterns of cross-reactivity among a panel of 21 variants and 15 groups of ... Full text Open Access 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

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

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

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

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

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

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

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

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

Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1.

Journal Article Front Immunol · 2023 INTRODUCTION: Neutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an ardu ... Full text Link to item Cite

Corrigendum: Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1.

Journal Article Front Immunol · 2023 [This corrects the article DOI: 10.3389/fimmu.2023.1271686.]. ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Boosting immunity to Omicron.

Journal Article Nat Med · March 2022 Full text Link to item Cite

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

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

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

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

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

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

Booster of mRNA-1273 Strengthens SARS-CoV-2 Omicron Neutralization.

Journal Article medRxiv · December 20, 2021 The Omicron variant of SARS-CoV-2 is raising concerns because of its increased transmissibility and potential for reduced susceptibility to antibody neutralization. To assess the potential risk of this variant to existing vaccines, serum samples from mRNA- ... 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Simian-Human Immunodeficiency Virus SHIV.CH505-Infected Infant and Adult Rhesus Macaques Exhibit Similar Env-Specific Antibody Kinetics, despite Distinct T-Follicular Helper and Germinal Center B Cell Landscapes.

Journal Article J Virol · August 1, 2019 Global elimination of pediatric human immunodeficiency virus (HIV) infections will require the development of novel immune-based approaches, and understanding infant immunity to HIV is critical to guide the rational design of these intervention strategies. ... 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

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 Featured Publication 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Journal Article J Virol · December 15, 2017 Featured Publication 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Journal Article Nat Med · July 2016 Featured Publication 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

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

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

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

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

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 Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Journal Article Nature · January 1, 2014 A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that ... Full text Open Access Cite

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

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

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

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

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

Journal Article Hum Vaccin Immunother · October 2013 We evaluated the immunogenicity and efficacy of Vaxfectin(®) adjuvanted SIV DNA vaccines in mice and macaques. Vaccination of mice with Vaxfectin(®) adjuvanted SIV gag DNA induced higher humoral immune responses than administration of unadjuvanted DNA, whe ... Full text Link to item Cite

A computational framework for the analysis of peptide microarray antibody binding data with application to HIV vaccine profiling.

Journal Article J Immunol Methods · September 30, 2013 We present an integrated analytical method for analyzing peptide microarray antibody binding data, from normalization through subject-specific positivity calls and data integration and visualization. Current techniques for the normalization of such data se ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Journal Article N Engl J Med · April 5, 2012 Featured Publication 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

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

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

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

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

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

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

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

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

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

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

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

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

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

New broadly neutralizing human monoclonal antibodies targeting the 2F5 epitope

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

Vaccine-Elicited IgG Subclasses and Functional Antibodies

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

Epitope Specificities of Elite Neutralizing Sera from HIV-1-Infected Individuals

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

Strategies for eliciting HIV-1 inhibitory antibodies.

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

Is developing an HIV-1 vaccine possible?

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

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

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

HIV-1 envelope induces memory B cell responses that correlate with plasma antibody levels after envelope gp120 protein vaccination or HIV-1 infection.

Journal Article J Immunol · August 15, 2009 Successful vaccines (i.e., tetanus and diphtheria) can induce long-lived Ab levels that are maintained by bone marrow plasma cells and plasma Ab levels do not correlate with numbers of blood memory B cells. Destruction of CD4(+) T cells early in HIV-1 acut ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

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

Antibody responses and virus escape: implications for HIV-1 vaccine and therapeutic design

Journal Article Future Virology · January 2006 HIV-1 can escape from neutralizing antibodies rapidly during natural infection. Evolution of antibody escape is an important consideration for both vaccine and therapeutic development. Recent studies highlight both the potential strength of specifi ... Full text Cite