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Barton Ford Haynes

Frederic M. Hanes Distinguished Professor of Medicine
Medicine, Duke Human Vaccine Institute
DUMC Box 103020, Durham, NC 27710
106 Research Drive, Msrbii 4090, Durham, NC 27710

Selected Publications


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

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

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

ARMADiLLO: a web server for analyzing antibody mutation probabilities.

Journal Article Nucleic Acids Res · July 5, 2023 Antibodies are generated by B cells that evolve receptor specificity to pathogens through rounds of mutation and selection in a process called affinity maturation. Somatic hypermutation is mediated by an enzyme with DNA sequence context-dependent targeting ... 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

COVID-19 Diagnosis and SARS-CoV-2 Strain Identification by a Rapid, Multiplexed, Point-of-Care Antibody Microarray.

Journal Article Anal Chem · April 4, 2023 Antigen tests to detect SARS-CoV-2 have emerged as a promising rapid diagnostic method for COVID-19, but they are unable to differentiate between variants of concern (VOCs). Here, we report a rapid point-of-care test (POC-T), termed CoVariant-SPOT, that us ... Full text Open Access 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

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

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

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

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

HIV-1 Vpu restricts Fc-mediated effector functions in vivo.

Journal Article Cell Rep · November 8, 2022 Non-neutralizing antibodies (nnAbs) can eliminate HIV-1-infected cells via antibody-dependent cellular cytotoxicity (ADCC) and were identified as a correlate of protection in the RV144 vaccine trial. Fc-mediated effector functions of nnAbs were recently sh ... 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

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

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

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

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

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

ARMADiLLO: a web server for analyzing antibody mutation probabilities.

Journal Article Nucleic Acids Res · July 5, 2023 Antibodies are generated by B cells that evolve receptor specificity to pathogens through rounds of mutation and selection in a process called affinity maturation. Somatic hypermutation is mediated by an enzyme with DNA sequence context-dependent targeting ... 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

COVID-19 Diagnosis and SARS-CoV-2 Strain Identification by a Rapid, Multiplexed, Point-of-Care Antibody Microarray.

Journal Article Anal Chem · April 4, 2023 Antigen tests to detect SARS-CoV-2 have emerged as a promising rapid diagnostic method for COVID-19, but they are unable to differentiate between variants of concern (VOCs). Here, we report a rapid point-of-care test (POC-T), termed CoVariant-SPOT, that us ... Full text Open Access 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

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

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

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

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

HIV-1 Vpu restricts Fc-mediated effector functions in vivo.

Journal Article Cell Rep · November 8, 2022 Non-neutralizing antibodies (nnAbs) can eliminate HIV-1-infected cells via antibody-dependent cellular cytotoxicity (ADCC) and were identified as a correlate of protection in the RV144 vaccine trial. Fc-mediated effector functions of nnAbs were recently sh ... 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

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

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

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

Journal Article Nature communications · October 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 Cite

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

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

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

Leveraging antigenic seniority for maternal vaccination to prevent mother-to-child transmission of HIV-1.

Journal Article NPJ Vaccines · July 30, 2022 The development of a maternal HIV vaccine to synergize with current antiretroviral drug prophylaxis can overcome implementation challenges and further reduce mother-to-child transmission (MTCT) of HIV. Both the epitope-specificity and autologous neutraliza ... Full text 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

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

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

SARS-CoV-2 Neutralizing Antibodies for COVID-19 Prevention and Treatment.

Journal Article Annu Rev Med · January 27, 2022 Prophylactic and therapeutic drugs are urgently needed to combat coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over the past year, SARS-CoV-2 neutralizing antibodies have been developed for prev ... Full text Link to item Cite

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

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

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

Journal Article Science translational medicine · January 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 Cite

Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center

Conference npj Vaccines · December 1, 2021 The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed tha ... Full text Cite

Strategies for eliciting multiple lineages of broadly neutralizing antibodies to HIV by vaccination.

Journal Article Curr Opin Virol · December 2021 A prophylactic vaccine would be a powerful tool in the fight against HIV. Passive immunization of animals with broadly neutralizing antibodies (bnAbs) affords protection against viral challenge, and recent data from the Antibody Mediated Prevention clinica ... Full text Link to item Cite

Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial.

Journal Article J Clin Invest · December 1, 2021 Naive and memory CD4+ T cells reactive with human immunodeficiency virus type 1 (HIV-1) are detectable in unexposed, unimmunized individuals. The contribution of preexisting CD4+ T cells to a primary immune response was investigated in 20 HIV-1-seronegativ ... Full text Link to item Cite

Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.

Journal Article Cell reports · November 2021 Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we is ... Full text 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

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

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

SARS-CoV-2 and HIV-1 - a tale of two vaccines.

Journal Article Nat Rev Immunol · September 2021 The rapid development of COVID-19 vaccines and their deployment in less than a year is a scientific and medical triumph that has raised a key question. Why do we have several SARS-CoV-2 vaccines but do not have a single HIV-1 vaccine? ... 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 Scientific reports · July 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 Cite

Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions.

Journal Article Cell Rep Med · June 15, 2021 The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample ... 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 ... Full text Open Access 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

New SHIVs and Improved Design Strategy for Modeling HIV-1 Transmission, Immunopathogenesis, Prevention and Cure.

Journal Article J Virol · May 10, 2021 Previously, we showed that substitution of HIV-1 Env residue 375-Ser by bulky aromatic residues enhances binding to rhesus CD4 and enables primary HIV-1 Envs to support efficient replication as simian-human immunodeficiency virus (SHIV) chimeras in rhesus ... Full text Open Access 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

Protein/AS01B vaccination elicits stronger, more Th2-skewed antigen-specific human T follicular helper cell responses than heterologous viral vectors.

Journal Article Cell Rep Med · March 16, 2021 Interactions between B cells and CD4+ T follicular helper (Tfh) cells are key determinants of humoral responses. Using samples from clinical trials performed with the malaria vaccine candidate antigen Plasmodium falciparum merozoite protein (PfRH5), we com ... Full text Link to item Cite

HIV mRNA Vaccines-Progress and Future Paths.

Journal Article Vaccines (Basel) · February 7, 2021 The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host's cells to manufacture protein immun ... Full text Link to item Cite

A New Vaccine to Battle Covid-19.

Journal Article N Engl J Med · February 4, 2021 Full text Link to item Cite

Vaccine Innovations - Past and Future.

Journal Article N Engl J Med · February 4, 2021 Full text Link to item Cite

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

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

Prospects for a safe COVID-19 vaccine.

Journal Article Sci Transl Med · November 4, 2020 Rapid development of an efficacious vaccine against the viral pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of the coronavirus disease 2019 (COVID-19) pandemic, is essential, but rigorous studies are required to determine ... 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

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

Journal Article bioRxiv · October 13, 2020 The SARS-CoV-2 spike (S) protein, a primary target for COVID-19 vaccine development, presents its Receptor Binding Domain in two conformations: receptor-accessible "up" or receptor-inaccessible "down" conformations. Here, we report that the commonly used s ... 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

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

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

Controlling the SARS-CoV-2 spike glycoprotein conformation.

Journal Article Nat Struct Mol Biol · October 2020 The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a ... Full text Link to item Cite

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

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

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

Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials.

Journal Article mSphere · June 3, 2020 A maternal vaccine capable of boosting neutralizing antibody (NAb) responses directed against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (En ... Full text Link to item Cite

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

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

Controlling the SARS-CoV-2 Spike Glycoprotein Conformation.

Journal Article bioRxiv · May 18, 2020 The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target ... 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

Conditional antibody expression to avoid central B cell deletion in humanized HIV-1 vaccine mouse models.

Journal Article Proc Natl Acad Sci U S A · April 7, 2020 HIV-1 vaccine development aims to elicit broadly neutralizing antibodies (bnAbs) against diverse viral strains. In some HIV-1-infected individuals, bnAbs evolved from precursor antibodies through affinity maturation. To induce bnAbs, a vaccine must mediate ... 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

Aberrant B cell repertoire selection associated with HIV neutralizing antibody breadth.

Journal Article Nat Immunol · February 2020 A goal of HIV vaccine development is to elicit antibodies with neutralizing breadth. Broadly neutralizing antibodies (bNAbs) to HIV often have unusual sequences with long heavy-chain complementarity-determining region loops, high somatic mutation rates and ... 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

Engineering immunity for next generation HIV vaccines: The intersection of bioengineering and immunology.

Journal Article Vaccine · January 10, 2020 Bioengineering approaches grounded in immunology have the potential for the discovery and development of a successful HIV vaccine. The overarching goal is to engineer immunity through a fusion of immunology with bioengineering to create novel strategies fo ... Full text Link to item Cite

Subordinate Effect of -21M HLA-B Dimorphism on NK Cell Repertoire Diversity and Function in HIV-1 Infected Individuals of African Origin.

Journal Article Front Immunol · 2020 Natural Killer (NK) cells play an important role in antiviral defense and their potent effector function identifies them as key candidates for immunotherapeutic interventions in chronic viral infections. Their remarkable functional agility is achieved by v ... 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

How does HIV env structure informs vaccine design?

Journal Article Microscopy and Microanalysis · January 1, 2020 Full text Cite

Cross-Reactivity to Kynureninase Tolerizes B Cells That Express the HIV-1 Broadly Neutralizing Antibody 2F5.

Journal Article J Immunol · December 15, 2019 2F5 is an HIV-1 broadly neutralizing Ab that also binds the autoantigens kynureninase (KYNU) and anionic lipids. Generation of 2F5-like Abs is proscribed by immune tolerance, but it is unclear which autospecificity is responsible. We sampled the BCR repert ... 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

Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection.

Journal Article Proc Natl Acad Sci U S A · December 3, 2019 Peptides generated by proteasome-catalyzed splicing of noncontiguous amino acid sequences have been shown to constitute a source of nontemplated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. ... 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

Multiple roles for HIV broadly neutralizing antibodies.

Journal Article Sci Transl Med · October 30, 2019 Potent broadly neutralizing antibodies may be used to treat or prevent HIV and to help guide HIV vaccine design. ... 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

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

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

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

The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template.

Journal Article Cell Rep · May 21, 2019 Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 ( ... Full text Link to item Cite

Self-tolerance curtails the B cell repertoire to microbial epitopes.

Journal Article JCI Insight · May 16, 2019 Immunological tolerance removes or inactivates self-reactive B cells, including those that also recognize cross-reactive foreign antigens. Whereas a few microbial pathogens exploit these "holes" in the B cell repertoire by mimicking host antigens to evade ... Full text Link to item Cite

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

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

Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.

Journal Article Immunity · March 19, 2019 Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual ... 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

Vaccine induction of antibodies and tissue-resident CD8+ T cells enhances protection against mucosal SHIV-infection in young macaques.

Journal Article JCI Insight · February 21, 2019 Antibodies and cytotoxic T cells represent 2 arms of host defense against pathogens. We hypothesized that vaccines that induce both high-magnitude CD8+ T cell responses and antibody responses might confer enhanced protection against HIV. To test this hypot ... Full text Link to item Cite

Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector.

Journal Article Viruses · February 15, 2019 A chimeric vesicular stomatitis virus with the glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, is a potent viral vaccine vector that overcomes several of the limitations of wild-type VSV. Here, we evaluated the potential of VSV-GP as an HIV ... 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

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.

Journal Article Cell Host Microbe · January 9, 2019 Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large vir ... 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

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

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

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

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

Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.

Journal Article Cell Rep · October 23, 2018 Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition. Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth. To understand the interp ... Full text Link to item Cite

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

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

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

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

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

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

Germline-targeting and Reverse Engineering to Elicit CH235.12 Lineage bNAbs

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2018 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

New SHIV Models of bNAb Elicitation and Env-Ab Coevolution

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

Increased Breadth of T-cell Responses After Mosaic HIV Vaccination in Humans (HVTN 106)

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

A CD4-mimetic compound enhances vaccine efficacy against stringent immunodeficiency virus challenge.

Journal Article Nat Commun · June 18, 2018 The envelope glycoprotein (Env) trimer ((gp120/gp41)3) mediates human immunodeficiency virus (HIV-1) entry into cells. The "closed," antibody-resistant Env trimer is driven to more open conformations by binding the host receptor, CD4. Broadly neutralizing ... Full text 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

Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection.

Journal Article Nat Commun · May 15, 2018 Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in ... Full text Link to item Cite

What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling.

Journal Article Cold Spring Harb Perspect Biol · May 1, 2018 A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have in ... 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

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

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

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

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

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

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

HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.

Journal Article Nat Commun · March 16, 2018 HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man9-V3") for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutraliz ... Full text Link to item Cite

Fine epitope signature of antibody neutralization breadth at the HIV-1 envelope CD4-binding site.

Journal Article JCI Insight · March 8, 2018 Major advances in donor identification, antigen probe design, and experimental methods to clone pathogen-specific antibodies have led to an exponential growth in the number of newly characterized broadly neutralizing antibodies (bnAbs) that recognize the H ... Full text Link to item Cite

Combination Adenovirus and Protein Vaccines Prevent Infection or Reduce Viral Burden after Heterologous Clade C Simian-Human Immunodeficiency Virus Mucosal Challenge.

Journal Article J Virol · January 15, 2018 HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of adenovirus (Ad) vectors expressing HIV 1086.C (clade C) envelope glycoprotein (Env), SIV Gag p55, and human pegiv ... Full text Link to item Cite

Cross-reactivity of HIV vaccine responses and the microbiome.

Journal Article Curr Opin HIV AIDS · January 2018 PURPOSE OF REVIEW: A successful human immunodeficiency virus-type 1 (HIV-1) vaccine will require immunogens that induce protective immune responses. However, recent studies suggest that the response to HIV-1 and perhaps other viruses may be altered by immu ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

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

Journal Article J Virol · December 15, 2017 An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia virus Ankara (MVA) ex ... Full text Link to item Cite

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

Development of a recombinant yellow fever vector expressing a HIV clade C founder envelope gp120.

Journal Article J Virol Methods · November 2017 Development of a HIV-1 vaccine is a major global priority. The yellow fever virus (YFV) attenuated vaccine 17D is among the most effective of currently used vaccines. However, the stability of the YFV17D vector when carrying non-flavivirus genes has been p ... Full text Link to item Cite

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

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

Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies.

Journal Article Proc Natl Acad Sci U S A · August 8, 2017 Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen- ... Full text Link to item Cite

HIV-1 Consensus Envelope-Induced Broadly Binding Antibodies.

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

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

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

Short Communication: Small-Molecule CD4 Mimetics Sensitize HIV-1-Infected Cells to Antibody-Dependent Cellular Cytotoxicity by Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Nonhuman Primates.

Journal Article AIDS Res Hum Retroviruses · May 2017 Recent studies have linked antibody Fc-mediated effector functions with control of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus infections. Interestingly, the presence of antibodies with potent antibody-dependent cellular c ... Full text Link to item Cite

Glycosylation Benchmark Profile for HIV-1 Envelope Glycoprotein Production Based on Eleven Env Trimers.

Journal Article J Virol · May 1, 2017 HIV-1 envelope glycoprotein (Env) glycosylation is important because individual glycans are components of multiple broadly neutralizing antibody epitopes, while shielding other sites that might otherwise be immunogenic. The glycosylation on Env is influenc ... Full text Link to item Cite

Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.

Journal Article Cell Rep · April 25, 2017 While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of ant ... Full text Link to item Cite

Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses.

Journal Article J Virol · April 1, 2017 HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid the exp ... Full text Link to item Cite

Developing an HIV vaccine.

Journal Article Science · March 17, 2017 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

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

Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.

Journal Article Nature · March 9, 2017 Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messen ... 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

BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance.

Journal Article Cell Rep · February 14, 2017 Activation-induced cytidine deaminase (AID) is required to purge autoreactive immature and transitional-1 (immature/T1) B cells at the first tolerance checkpoint, but how AID selectively removes self-reactive B cells is unclear. We now show that B cell ant ... Full text Link to item Cite

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

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

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

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

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

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

Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness.

Journal Article Proc Natl Acad Sci U S A · January 24, 2017 Sexual transmission of HIV-1 is an inefficient process, with only one or few variants of the donor quasispecies establishing the new infection. A critical, and as yet unresolved, question is whether the mucosal bottleneck selects for viruses with increased ... Full text Link to item Cite

Systemic administration of an HIV-1 broadly neutralizing dimeric IgA yields mucosal secretory IgA and virus neutralization.

Journal Article Mucosal Immunol · January 2017 We investigated the mucosal distribution and neutralization potency of rhesus recombinant versions of the HIV-specific, broadly neutralizing antibody b12 (RhB12) following intravenous administration to lactating rhesus monkeys. IgG and dimeric IgA (dIgA) a ... Full text Link to item Cite

Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies.

Journal Article J Virol · January 1, 2017 UNLABELLED: Definition of the key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue may prove critical to effective vaccine development and the prophylactic use of monoclonal antibodies. Although direct antibody-me ... Full text Link to item Cite

Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting.

Journal Article PLoS Pathog · January 2017 Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve p ... Full text Link to item Cite

Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development.

Journal Article Immunol Rev · January 2017 Induction of HIV-1 broadly neutralizing antibodies (bnAbs) to date has only been observed in the setting of HIV-1 infection, and then only years after HIV transmission. Thus, the concept has emerged that one path to induction of bnAbs is to define the vira ... Full text Link to item Cite

Host controls of HIV broadly neutralizing antibody development.

Journal Article Immunol Rev · January 2017 Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced in the setting of vaccination. Considerable progress has been ma ... Full text Link to item Cite

The quest for an antibody-based HIV vaccine.

Journal Article Immunol Rev · January 2017 Despite major advances in our understanding of the biology of HIV-1 infection, and advances in antiretroviral therapy to treat the disease, there were 2.1 million new cases of HIV-1 infection in 2015, and 36.7 million people living with AIDS (http://www.un ... Full text Link to item Cite

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

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

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

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

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

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

HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism.

Journal Article J Immunol · December 15, 2016 The HIV-1 envelope protein (Env) has evolved to subvert the host immune system, hindering viral control by the host. The tryptophan metabolic enzyme kynureninase (KYNU) is mimicked by a portion of the HIV Env gp41 membrane proximal region (MPER) and is cro ... Full text Link to item Cite

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

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

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

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

Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain.

Journal Article Nat Med · December 2016 For broad protection against infection by viruses such as influenza or HIV, vaccines should elicit antibodies that bind conserved viral epitopes, such as the receptor-binding site (RBS). RBS-directed antibodies have been described for both HIV and influenz ... Full text Link to item Cite

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

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

Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth.

Journal Article Immunity · November 15, 2016 Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, ... 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

Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity.

Journal Article EBioMedicine · October 2016 Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1) viruses or rare cases of vaccine-matched neutralization-resistant (tier-2) viruses, but no vaccine has induced antibodies that can broadly neutralize heter ... Full text Link to item Cite

Initiation of Neutralizing Antibody B Cell Lineages by HIV Vaccine Candidates

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2016 Link to item Cite

Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.

Journal Article Cell · September 8, 2016 The design of immunogens that elicit broadly reactive neutralizing antibodies (bnAbs) has been a major obstacle to HIV-1 vaccine development. One approach to assess potential immunogens is to use mice expressing precursors of human bnAbs as vaccination mod ... Full text Link to item Cite

Novel Monoclonal Antibodies for Studies of Human and Rhesus Macaque Secretory Component and Human J-Chain.

Journal Article Monoclon Antib Immunodiagn Immunother · August 2016 Immunoglobulin A (IgA) antibodies exist in monomeric, dimeric, and secretory forms. Dimerization of IgA depends on a 15-kD polypeptide termed "joining (J) chain," which is also part of the binding site for an epithelial glycoprotein called "secretory compo ... Full text Link to item Cite

Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection.

Journal Article PLoS Pathog · August 2016 The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is un ... Full text Link to item Cite

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

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

Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies.

Journal Article Sci Immunol · July 29, 2016 Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. bnAbs occur in some HIV-1-infected individuals and frequently have characteristics of autoantibodies. We have studied cohorts of HIV-1-infected individuals who mad ... Full text Link to item Cite

Latency reversal and viral clearance to cure HIV-1.

Journal Article Science · July 22, 2016 Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted ... Full text Link to item Cite

Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design.

Journal Article J Virol · July 1, 2016 UNLABELLED: Extraordinary antibodies capable of near pan-neutralization of HIV-1 have been identified. One of the broadest is antibody 10E8, which recognizes the membrane-proximal external region (MPER) of the HIV-1 envelope and neutralizes >95% of circula ... 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

A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.

Journal Article Cell Rep · May 17, 2016 Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. ... Full text Open Access Link to item Cite

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

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

Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds.

Journal Article J Virol · May 15, 2016 UNLABELLED: The human immunodeficiency virus (HIV-1) envelope glycoproteins (Env) mediate virus entry through a series of complex conformational changes triggered by binding to the receptors CD4 and CCR5/CXCR4. Broadly neutralizing antibodies that recogniz ... Full text Link to item Cite

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

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

Cogan's syndrome

Chapter · April 19, 2016 Cite

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Journal Article Cell · April 7, 2016 Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived a ... Full text Link to item Cite

HIV-Host Interactions: Implications for Vaccine Design.

Journal Article Cell Host Microbe · March 9, 2016 Development of an effective AIDS vaccine is a global priority. However, the extreme diversity of HIV type 1 (HIV-1), which is a consequence of its propensity to mutate to escape immune responses, along with host factors that prevent the elicitation of prot ... Full text Link to item Cite

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

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

HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence.

Journal Article Immunogenetics · February 2016 Complementarity Determining Region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen-binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment ... Full text Link to item Cite

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

Journal Article Cell Rep · January 5, 2016 Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induc ... Full text Link to item Cite

New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency.

Journal Article J Virol · January 1, 2016 UNLABELLED: The epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development of these antibodies are providing insights for vaccination strategies. In addition, th ... Full text Link to item Cite

Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.

Journal Article Nat Struct Mol Biol · January 2016 Broadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we ... Full text Link to item Cite

Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8.

Journal Article PLoS One · 2016 Antibody 10E8 targets the membrane-proximal external region (MPER) of HIV-1 gp41, neutralizes >97% of HIV-1 isolates, and lacks the auto-reactivity often associated with MPER-directed antibodies. The developmental pathway of 10E8 might therefore serve as a ... Full text Link to item Cite

Generation and Characterization of a Bivalent HIV-1 Subtype C gp120 Protein Boost for Proof-of-Concept HIV Vaccine Efficacy Trials in Southern Africa.

Journal Article PLoS One · 2016 The viral envelope glycoprotein (Env) is the major target for antibody (Ab)-mediated vaccine development against the Human Immunodeficiency Virus type 1 (HIV-1). Although several recombinant Env antigens have been evaluated in clinical trials, only the sur ... Full text Link to item Cite

E-103 The pathway to HIV vaccine development

Conference JAIDS Journal of Acquired Immune Deficiency Syndromes · January 2016 Full text Cite

Immunogenic Stimulus for Germline Precursors of Antibodies that Engage the Influenza Hemagglutinin Receptor-Binding Site.

Journal Article Cell Rep · December 29, 2015 Influenza-virus antigenicity evolves to escape host immune protection. Antibody lineages within individuals evolve in turn to increase affinity and hence potency. Strategies for a "universal" influenza vaccine to elicit lineages that escape this evolutiona ... Full text Link to item Cite

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

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

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants.

Journal Article Viruses · October 21, 2015 Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that gener ... Full text Link to item Cite

Immune correlates of vaccine protection against HIV-1 acquisition.

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

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

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

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

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

Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research.

Journal Article J Virol · August 2015 UNLABELLED: Eliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations in envelope (Env) subtype and structure. The majority of new global HIV-1 ... Full text Link to item Cite

Inhibitory Effect of Individual or Combinations of Broadly Neutralizing Antibodies and Antiviral Reagents against Cell-Free and Cell-to-Cell HIV-1 Transmission.

Journal Article J Virol · August 2015 UNLABELLED: To date, most therapeutic and vaccine candidates for human immunodeficiency virus type 1 (HIV-1) are evaluated preclinically for efficacy against cell-free viral challenges. However, cell-associated HIV-1 is suggested to be a major contributor ... Full text Link to item Cite

New approaches to HIV vaccine development.

Journal Article Curr Opin Immunol · August 2015 Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration ... 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

Stable Expression of Lentiviral Antigens by Quality-Controlled Recombinant Mycobacterium bovis BCG Vectors.

Journal Article Clin Vaccine Immunol · July 2015 The well-established safety profile of the tuberculosis vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), makes it an attractive vehicle for heterologous expression of antigens from clinically relevant pathogens. However, successful genera ... Full text Link to item Cite

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

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

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

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

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.

Journal Article Cell · June 4, 2015 The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site ... 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

Eliminating antibody polyreactivity through addition of N-linked glycosylation.

Journal Article Protein Sci · June 2015 Antibody polyreactivity can be an obstacle to translating a candidate antibody into a clinical product. Standard tests such as antibody binding to cardiolipin, HEp-2 cells, or nuclear antigens provide measures of polyreactivity, but its causes and the mean ... Full text Link to item Cite

Designing synthetic vaccines for HIV.

Journal Article Expert Rev Vaccines · June 2015 Despite three decades of intensive research efforts, the development of an effective prophylactic vaccine against HIV remains an unrealized goal in the global campaign to contain the HIV/AIDS pandemic. Recent characterization of novel epitopes for inducing ... Full text Link to item Cite

Viral receptor-binding site antibodies with diverse germline origins.

Journal Article Cell · May 21, 2015 Vaccines for rapidly evolving pathogens will confer lasting immunity if they elicit antibodies recognizing conserved epitopes, such as a receptor-binding site (RBS). From characteristics of an influenza-virus RBS-directed antibody, we devised a signature m ... Full text Link to item Cite

CD4 mimetics sensitize HIV-1-infected cells to ADCC.

Journal Article Proc Natl Acad Sci U S A · May 19, 2015 HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure o ... Full text Link to item Cite

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

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

Key mutations stabilize antigen-binding conformation during affinity maturation of a broadly neutralizing influenza antibody lineage.

Journal Article Proteins · April 2015 Featured Publication Affinity maturation, the process in which somatic hypermutation and positive selection generate antibodies with increasing affinity for an antigen, is pivotal in acquired humoral immunity. We have studied the mechanism of affinity gain in a human B-cell li ... Full text Link to item Cite

Key mutations stabilize antigen-binding conformation during affinity maturation of a broadly neutralizing influenza antibody lineage

Journal Article Proteins: Structure, Function and Bioinformatics · April 1, 2015 Affinity maturation, the process in which somatic hypermutation and positive selection generate antibodies with increasing affinity for an antigen, is pivotal in acquired humoral immunity. We have studied the mechanism of affinity gain in a human B-cell li ... Full text Cite

A new model for catalyzing translational science: the early stage investigator mentored research scholar program in HIV vaccines.

Journal Article Clin Transl Sci · April 2015 Engagement of early stage investigators (ESIs) in the search for a safe and effective vaccine is critical to the success of this highly challenging endeavor. In the wake of disappointing results from a large-scale efficacy trial, the HIV Vaccine Trials Net ... Full text Link to item Cite

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

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

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

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

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

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

Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes.

Journal Article Virology · January 15, 2015 Featured Publication Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 env genes from chronically-infect ... Full text Open Access Link to item Cite

Polyreactivity and autoreactivity among HIV-1 antibodies.

Journal Article J Virol · January 2015 Featured Publication UNLABELLED: It is generally acknowledged that human broadly neutralizing antibodies (bNAbs) capable of neutralizing multiple HIV-1 clades are often polyreactive or autoreactive. Whereas polyreactivity or autoreactivity has been proposed to be crucial for n ... 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

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

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

Gene deletions in Mycobacterium bovis BCG stimulate increased CD8+ T cell responses.

Journal Article Infect Immun · December 2014 Featured Publication Mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host's immune response. It has been suggested that mycobacteria may contain genes that reduce th ... Full text Link to item Cite

Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation.

Journal Article Retrovirology · November 19, 2014 BACKGROUND: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 ... Full text Open Access Link to item Cite

Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface.

Journal Article Nature · November 6, 2014 Featured Publication The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22 ... Full text Link to item Cite

Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo.

Journal Article J Virol · November 2014 Featured Publication UNLABELLED: Over the past 5 years, a new generation of highly potent and broadly neutralizing HIV-1 antibodies has been identified. These antibodies can protect against lentiviral infection in nonhuman primates (NHPs), suggesting that passive antibody tran ... 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

E-102 Advances in Prophylactic HIV Vaccine Development

Conference JAIDS Journal of Acquired Immune Deficiency Syndromes · November 2014 Full text Cite

Structure and immune recognition of trimeric pre-fusion HIV-1 Env.

Journal Article Nature · October 23, 2014 Featured Publication The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediat ... 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

Recombinant Mycobacterium bovis bacillus Calmette-Guérin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques.

Journal Article Clin Vaccine Immunol · October 2014 Featured Publication Live attenuated nonpathogenic Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. These c ... Full text Link to item Cite

Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies.

Journal Article Cell Host Microbe · September 10, 2014 Featured Publication Induction of HIV-1 broad neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development but has remained challenging partially due to unusual traits of bnAbs, including high somatic hypermutation (SHM) frequencies and in-frame insertions and deleti ... Full text Link to item Cite

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

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

Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users.

Journal Article Open Forum Infect Dis · September 2014 BACKGROUND: We performed human immunodeficiency virus type 1 (HIV-1) transmitted/founder (T/F) virus analysis of the VAX003 vaccine efficacy trial participants to characterize the transmission bottleneck and test for vaccine-associated reduction or enhance ... Full text Link to item Cite

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

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

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

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

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

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

Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains.

Journal Article Proc Natl Acad Sci U S A · July 15, 2014 Featured Publication Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody a ... Full text Link to item Cite

Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements.

Journal Article Cell Host Microbe · July 9, 2014 B cells produce a diverse antibody repertoire by undergoing gene rearrangements. Pathogen exposure induces the clonal expansion of B cells expressing antibodies that can bind the infectious agent. To assess human B cell responses to trivalent seasonal infl ... Full text Link to item Cite

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

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

The Center for HIV/AIDS Vaccine Immunology (CHAVI) multi-site quality assurance program for cryopreserved human peripheral blood mononuclear cells.

Journal Article J Immunol Methods · July 2014 The Center for HIV/AIDS Vaccine Immunology (CHAVI) consortium was established to determine the host and virus factors associated with HIV transmission, infection and containment of virus replication, with the goal of advancing the development of an HIV pro ... Full text Open Access Link to item Cite

Progress in HIV-1 vaccine development.

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

Cross-reactive potential of human T-lymphocyte responses in HIV-1 infection.

Journal Article Vaccine · June 30, 2014 Featured Publication An effective HIV-1 vaccine should elicit sufficient breadth of immune recognition to protect against the genetically diverse forms of the circulating virus. Evaluation of the breadth and magnitude of cellular immune responses to epitope variants is importa ... Full text Link to item Cite

Redemption of autoreactive B cells.

Journal Article Proc Natl Acad Sci U S A · June 24, 2014 Featured Publication Full text Link to item Cite

CD4-mimetic small molecules sensitize human immunodeficiency virus to vaccine-elicited antibodies.

Journal Article J Virol · June 2014 Featured Publication UNLABELLED: Approaches to prevent human immunodeficiency virus (HIV-1) transmission are urgently needed. Difficulties in eliciting antibodies that bind conserved epitopes exposed on the unliganded conformation of the HIV-1 envelope glycoprotein (Env) trime ... Full text Link to item Cite

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

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

AIDS/HIV. Host controls of HIV neutralizing antibodies.

Journal Article Science · May 9, 2014 Featured Publication The unusual traits of broadly neutralizing antibodies for HIV-1 are stimulating new strategies to induce their production through vaccination. ... Full text Link to item Cite

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

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

HIV broadly neutrizing antibodies and immunological tolerance

Journal Article JOURNAL OF IMMUNOLOGY · May 1, 2014 Link to item Cite

DH reading frame usage influences HIV-1 epitope recognition

Journal Article JOURNAL OF IMMUNOLOGY · May 1, 2014 Link to item Cite

Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes.

Journal Article J Immunol · April 1, 2014 Featured Publication We have shown that the protective HIV-1 Ab, 2F5, avidly reacts with a conserved mammalian self-Ag, kynureninase, and that the development of B cells specific for the 2F5 epitope is constrained by immunological tolerance. These observations suggest that the ... Full text Link to item Cite

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

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

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

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

Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity.

Journal Article J Virol · March 2014 Featured Publication UNLABELLED: Anti-HIV-1 envelope glycoprotein (Env) antibodies without broadly neutralizing activity correlated with protection in the RV144 clinical trial, stimulating interest in other protective mechanisms involving antibodies, such as antibody-dependent ... Full text Link to item Cite

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

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

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

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

Immune System Regulation in the Induction of Broadly Neutralizing HIV-1 Antibodies.

Journal Article Vaccines (Basel) · March 2014 In this brief review, we discuss immune tolerance as a factor that determines the magnitude and quality of serum antibody responses to HIV-1 infection and vaccination in the context of recent work. We propose that many conserved, neutralizing epitopes of H ... Full text Link to item Cite

Modulation of nonneutralizing HIV-1 gp41 responses by an MHC-restricted TH epitope overlapping those of membrane proximal external region broadly neutralizing antibodies.

Journal Article J Immunol · February 15, 2014 Featured Publication A goal of HIV-1 vaccine development is to elicit broadly neutralizing Abs (BnAbs), but current immunization strategies fail to induce BnAbs, and for unknown reasons, often induce nonneutralizing Abs instead. To explore potential host genetic contributions ... Full text Link to item Cite

Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.

Journal Article Proc Natl Acad Sci U S A · January 28, 2014 Featured Publication The membrane proximal external region (MPER) of HIV-1 glycoprotein (gp) 41 is involved in viral-host cell membrane fusion. It contains short amino acid sequences that are binding sites for the HIV-1 broadly neutralizing antibodies 2F5, 4E10, and 10E8, maki ... Full text Link to item Cite

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

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

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

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

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

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

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

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

Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

Journal Article PLoS One · 2014 Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to ... Full text Link to item Cite

Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation

Journal Article Retrovirology · 2014 © 2014 Liu et al.; licensee BioMed Central Ltd.Background: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, t ... Full text Cite

Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors.

Journal Article Proc Natl Acad Sci U S A · November 5, 2013 Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. Broadly neutralizing antibodies (BnAbs) are not induced by current vaccines, but are found in plasma in ∼20% of HIV-1-infected individuals after several years of infection. One strategy ... Full text Link to item Cite

Neutralizing IgG at the portal of infection mediates protection against vaginal simian/human immunodeficiency virus challenge.

Journal Article J Virol · November 2013 Neutralizing antibodies may have critical importance in immunity against human immunodeficiency virus type 1 (HIV-1) infection. However, the amount of protective antibody needed at mucosal surfaces has not been fully established. Here, we evaluated systemi ... Full text Link to item Cite

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

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

Genetic and Immunological Evidence for a Role of Env-V3 Antibodies in the RV144 Trial

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

Eliminating Autoreactivity of Variants of Antibody VRC07 by Glycan Masking

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

Human HIV-1 Vaccine Induced Antibody Durability and Env IgG3 Responses

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

Development of an Early Stage Investigator Scholar Program for Preclinical Researchers

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

Chemical synthesis of highly congested gp120 V1V2 N-glycopeptide antigens for potential HIV-1-directed vaccines.

Journal Article J Am Chem Soc · September 4, 2013 Critical to the search for an effective HIV-1 vaccine is the development of immunogens capable of inducing broadly neutralizing antibodies (BnAbs). A key first step in this process is to design immunogens that can be recognized by known BnAbs. The monoclon ... Full text Link to item Cite

Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice: selection against membrane proximal external region-associated autoreactivity limits T-dependent responses.

Journal Article J Immunol · September 1, 2013 A goal of HIV-1 vaccine development is to elicit broadly neutralizing Abs (BnAbs). Using a knock-in (KI) model of 2F5, a human HIV-1 gp41 membrane proximal external region (MPER)-specific BnAb, we previously demonstrated that a key obstacle to BnAb inducti ... Full text Link to item Cite

Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies.

Journal Article Immunity · August 22, 2013 Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make el ... Full text Link to item Cite

Common tolerance mechanisms, but distinct cross-reactivities associated with gp41 and lipids, limit production of HIV-1 broad neutralizing antibodies 2F5 and 4E10.

Journal Article J Immunol · August 1, 2013 Developing an HIV-1 vaccine has been hampered by the inability of immunogens to induce broadly neutralizing Abs (BnAbs) that protect against infection. Previously, we used knockin (KI) mice expressing a prototypical gp41-specific BnAb, 2F5, to demonstrate ... Full text Link to item Cite

Quantitative and qualitative differences in the T cell response to HIV in uninfected Ugandans exposed or unexposed to HIV-infected partners.

Journal Article J Virol · August 2013 HIV-exposed and yet persistently uninfected individuals have been an intriguing, repeated observation in multiple studies, but uncertainty persists on the significance and implications of this in devising protective strategies against HIV. We carried out a ... Full text Link to item Cite

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

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

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

Journal Article J Virol · July 2013 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

Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.

Journal Article Nat Struct Mol Biol · July 2013 HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to acco ... Full text Link to item Cite

Progress in HIV-1 vaccine development.

Journal Article Curr Opin HIV AIDS · July 2013 PURPOSE OF REVIEW: In this review, examples of recent progress in HIV-1 vaccine research are discussed. RECENT FINDINGS: New insights from the immune correlates analyses of the RV144 efficacy trial have accelerated vaccine development with leads to follow ... Full text Link to item Cite

HIV-1 neutralizing antibodies: understanding nature's pathways.

Journal Article Immunol Rev · July 2013 The development of an effective vaccine has been hindered by the enormous diversity of human immunodeficiency virus-1 (HIV-1) and its ability to escape a myriad of host immune responses. In addition, conserved vulnerable regions on the HIV-1 envelope glyco ... Full text Link to item Cite

Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design.

Journal Article J Virol · July 2013 Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and ... Full text Link to item Cite

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

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

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

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

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

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

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.

Journal Article Hum Mol Genet · May 1, 2013 Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated fact ... Full text Link to item Cite

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.

Journal Article Nature · April 25, 2013 Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide ... Full text Open Access Link to item Cite

Phenotypic properties of transmitted founder HIV-1.

Journal Article Proc Natl Acad Sci U S A · April 23, 2013 Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify ... Full text Open Access Link to item Cite

Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains.

Journal Article Proc Natl Acad Sci U S A · April 16, 2013 Next-generation sequencing of antibody transcripts from HIV-1-infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing an ... Full text Link to item Cite

Identification of Three Distinct Epitope Regions in the V2 Portion of gp120

Conference JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES · April 1, 2013 Link to item Cite

Analysis of Broad Neutralizing B Cell Lineages to Guide HIV-1 Immunogen Design

Conference JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES · April 1, 2013 Link to item Cite

Antigenicity and immunogenicity of transmitted/founder, consensus, and chronic envelope glycoproteins of human immunodeficiency virus type 1.

Journal Article J Virol · April 2013 Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins were examined for their ability to bind human anti-HIV-1 monoclonal antibodies (MAbs) and then used ... Full text Link to item Cite

Characterization of host-cell line specific glycosylation profiles of early transmitted/founder HIV-1 gp120 envelope proteins.

Journal Article J Proteome Res · March 1, 2013 Glycosylation plays an essential role in regulating protein function by modulating biological, structural, and therapeutic properties. However, due to its inherent heterogeneity and diversity, the comprehensive analysis of protein glycosylation remains a c ... Full text Link to item Cite

Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies.

Journal Article J Exp Med · February 11, 2013 Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation of neutralizing antibodies to the 2F5 and 4E10 epitopes of HIV-1 gp41 in man may be proscribed by i ... Full text Open Access Link to item Cite

Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones.

Journal Article Virology · February 5, 2013 We report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all T/F virus ... Full text Link to item Cite

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

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

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

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

Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants.

Journal Article Retrovirology · January 10, 2013 BACKGROUND: Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmit ... Full text Open Access Link to item Cite

Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.

Journal Article Proc Natl Acad Sci U S A · January 2, 2013 Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized w ... Full text Link to item Cite

Pre-clinical development of a recombinant, replication-competent adenovirus serotype 4 vector vaccine expressing HIV-1 envelope 1086 clade C.

Journal Article PLoS One · 2013 BACKGROUND: There is a well-acknowledged need for an effective AIDS vaccine that protects against HIV-1 infection or limits in vivo viral replication. The objective of these studies is to develop a replication-competent, vaccine vector based on the adenovi ... Full text Link to item Cite

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

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

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 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

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

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

HIV-1 infection-induced apoptotic microparticles inhibit human DCs via CD44.

Journal Article J Clin Invest · December 2012 Acute HIV-1 infection results in dysregulated immunity, which contributes to poor control of viral infection. DCs are key regulators of both adaptive and innate immune responses needed for controlling HIV-1, and we surmised that factors elicited during acu ... Full text Link to item Cite

Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.

Journal Article Nature · November 15, 2012 Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of ... Full text Link to item Cite

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

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

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

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

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

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

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

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

Enhanced priming of adaptive immunity by Mycobacterium smegmatis mutants with high-level protein secretion.

Journal Article Clin Vaccine Immunol · September 2012 Mycobacteria have features that make them attractive as potential vaccine vectors. The nonpathogenic and rapidly growing Mycobacterium smegmatis can express both Mycobacterium tuberculosis antigens and heterologous antigens from other pathogens, and it has ... Full text Link to item Cite

A tribute to Norman L. Letvin (1949–2012)

Journal Article Journal of Clinical Investigation · August 1, 2012 Full text Cite

A short segment of the HIV-1 gp120 V1/V2 region is a major determinant of resistance to V1/V2 neutralizing antibodies.

Journal Article J Virol · August 2012 Antibody PG9 is a prototypical member of a class of V1/V2-directed antibodies that effectively neutralizes diverse strains of HIV-1. We analyzed strain-specific resistance to PG9 using sequence and structural information. For multiply resistant strains, mu ... Full text Link to item Cite

Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials.

Journal Article J Infect Dis · August 1, 2012 BACKGROUND: A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection ... Full text Link to item Cite

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

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

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

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

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

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

B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study.

Journal Article Nat Biotechnol · May 7, 2012 Failure of immunization with the HIV-1 envelope to induce broadly neutralizing antibodies against conserved epitopes is a major barrier to producing a preventive HIV-1 vaccine. Broadly neutralizing monoclonal antibodies (BnAbs) from those subjects who do p ... Full text Link to item Cite

Lessons learned from HIV-1 vaccine trials: new priorities and directions.

Journal Article Nat Immunol · April 18, 2012 A vaccine against human immunodeficiency virus (HIV) seems to be on the horizon. Correlates of risk of infection for [corrected] the RV144 vaccine trial have been found. There is understanding of what makes HIV envelope-specific antibodies broadly neutrali ... Full text Link to item Cite

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

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

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

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

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

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

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

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

Generation of transmitted/founder HIV-1 infectious molecular clones and characterization of their replication capacity in CD4 T lymphocytes and monocyte-derived macrophages.

Journal Article J Virol · March 2012 Genome sequences of transmitted/founder (T/F) HIV-1 have been inferred by analyzing single genome amplicons of acute infection plasma viral RNA in the context of a mathematical model of random virus evolution; however, few of these T/F sequences have been ... Full text Link to item Cite

Enhanced outgrowth of EBV-transformed chronic lymphocytic leukemia B cells mediated by coculture with macrophage feeder cells.

Journal Article Blood · February 16, 2012 B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the clonal expansion of CD5-expressing B lymphocytes that produce mAbs often reactive with microbial or autoantigens. Long-term culture of B-CLL clones would permit the collection and characte ... Full text Link to item Cite

High-mannose glycan-dependent epitopes are frequently targeted in broad neutralizing antibody responses during human immunodeficiency virus type 1 infection.

Journal Article J Virol · February 2012 Broad and potent neutralizing antibody (BNAb) responses are rare in people infected by human immunodeficiency virus type 1 (HIV-1). Clearly defining the nature of BNAb epitopes on HIV-1 envelope glycoproteins (Envs) targeted in vivo is critical for future ... Full text Link to item Cite

Transcriptional network predicts viral set point during acute HIV-1 infection.

Journal Article J Am Med Inform Assoc · 2012 BACKGROUND: HIV-1-infected individuals with higher viral set points progress to AIDS more rapidly than those with lower set points. Predicting viral set point early following infection can contribute to our understanding of early control of HIV-1 replicati ... Full text Link to item Cite

Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.

Journal Article PLoS Pathog · 2012 Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottle ... Full text Link to item Cite

Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape.

Journal Article PLoS Pathog · 2012 Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, ... Full text Link to item Cite

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

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

Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.

Journal Article PLoS Pathog · 2012 A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma vi ... Full text Open Access Link to item Cite

Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.

Journal Article Nature · November 23, 2011 Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. H ... Full text Open Access Link to item Cite

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

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

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

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

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

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

Copy number variation of KIR genes influences HIV-1 control.

Journal Article PLoS Biol · November 2011 A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of ... Full text Link to item Cite

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

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

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

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

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

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

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

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

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

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

Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls.

Journal Article J Immunol · October 1, 2011 The HIV-1 broadly neutralizing Ab (bnAb) 2F5 has been shown to be poly-/self-reactive in vitro, and we previously demonstrated that targeted expression of its VDJ rearrangement alone was sufficient to trigger a profound B cell developmental blockade in 2F5 ... Full text Link to item Cite

HIV-1 gp120 V1V2-Scaffolds for Structural Analysis and Immunogen Design

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2011 Link to item Cite

Detection of CD4-Binding Site Antibodies in Three HIV-1 Seroconverter Cohorts

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2011 Link to item Cite

V2-Reactive Antibodies in RV144 Vaccinees' Plasma

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2011 Link to item Cite

Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.

Journal Article Science · September 16, 2011 Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies fro ... Full text Link to item Cite

Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody VRC01.

Journal Article J Virol · September 2011 The structure of VRC01 in complex with the HIV-1 gp120 core reveals that this broadly neutralizing CD4 binding site (CD4bs) antibody partially mimics the interaction of the primary virus receptor, CD4, with gp120. Here, we extended the investigation of the ... Full text Link to item Cite

Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins.

Journal Article J Virol · September 2011 Sexual transmission of human immunodeficiency virus type 1 (HIV-1) across mucosal barriers is responsible for the vast majority of new infections. This relatively inefficient process results in the transmission of a single transmitted/founder (T/F) virus, ... Full text Link to item Cite

epitopes immediately below the base of the V3 loop of gp120 as targets for the initial autologous neutralizing antibody response in two HIV-1 subtype B-infected individuals.

Journal Article J Virol · September 2011 Epitopes that drive the initial autologous neutralizing antibody response in HIV-1-infected individuals could provide insights for vaccine design. Although highly strain specific, these epitopes are immunogenic, vulnerable to antibody attack on infectious ... Full text Link to item Cite

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

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

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

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

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

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

Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin.

Journal Article Proc Natl Acad Sci U S A · August 23, 2011 Seasonal antigenic drift of circulating influenza virus leads to a requirement for frequent changes in vaccine composition, because exposure or vaccination elicits human antibodies with limited cross-neutralization of drifted strains. We describe a human m ... Full text Link to item Cite

Methods development for Analysis of Partially Deglycosylated Proteins and Application to an HIV Envelope Protein Vaccine Candidate.

Journal Article Int J Mass Spectrom · August 2011 The work presented herein describes the first comprehensive analysis of a partially deglycosylated HIV vaccine candidate envelope protein (Env). The Env, JRFL gp140 ΔCF, with 27 potential glycosylation sites, was partially deglycosylated with PNGase F as p ... Full text Link to item Cite

Correction: Thy1 Nk Cells from Vaccinia Virus-Primed Mice Confer Protection against Vaccinia Virus Challenge in the Absence of Adaptive Lymphocytes.

Journal Article PLoS pathogens · August 2011 [This corrects the article on p. e1002141 in vol. 7.]. ... Full text Cite

Characterization of glycosylation profiles of HIV-1 transmitted/founder envelopes by mass spectrometry.

Journal Article J Virol · August 2011 The analysis of HIV-1 envelope carbohydrates is critical to understanding their roles in HIV-1 transmission as well as in binding of envelope to HIV-1 antibodies. However, direct analysis of protein glycosylation by glycopeptide-based mass mapping approach ... Full text Link to item Cite

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

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

Thy1+ NK [corrected] cells from vaccinia virus-primed mice confer protection against vaccinia virus challenge in the absence of adaptive lymphocytes.

Journal Article PLoS Pathog · August 2011 While immunological memory has long been considered the province of T- and B-lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated i ... Full text Link to item Cite

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

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

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

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

Role of immune mechanisms in induction of HIV-1 broadly neutralizing antibodies.

Journal Article Curr Opin Immunol · June 2011 Although antibodies can be elicited by HIV-1 infection or immunization, those that are broadly neutralizing (bnAbs) are undetectable in most individuals, and when they do arise in HIV-1 infection, only do so years after transmission. Until recently, the re ... Full text Link to item Cite

Acute HIV-1 Infection.

Journal Article N Engl J Med · May 19, 2011 In 2009, the United Nations Estimated that 33.2 Million People worldwide were living with human immunodeficiency virus type 1 (HIV-1) infection and that 2.6 million people had been newly infected. The need for effective HIV-1 prevention has never been grea ... Full text Link to item Cite

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

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

HIV-1 vaccines and adaptive trial designs.

Journal Article Sci Transl Med · April 20, 2011 Developing a vaccine against the human immunodeficiency virus (HIV) poses an exceptional challenge. There are no documented cases of immune-mediated clearance of HIV from an infected individual, and no known correlates of immune protection. Although nonhum ... Full text Link to item Cite

Differences in HIV-specific T cell responses between HIV-exposed and -unexposed HIV-seronegative individuals.

Journal Article J Virol · April 2011 HIV-1-specific T lymphocyte responses in individuals exposed to HIV-1 but who remain persistently seronegative (HESNs) have been reported in some but not all previous studies. This study was designed to resolve unequivocally the question of whether HESNs m ... Full text Link to item Cite

Intranasal vaccination with the recombinant Listeria monocytogenes ΔactA prfA* mutant elicits robust systemic and pulmonary cellular responses and secretory mucosal IgA.

Journal Article Clin Vaccine Immunol · April 2011 We previously showed that recombinant (r) Listeria monocytogenes carrying ΔactA and a selected prfA* mutation (r-Listeria ΔactA prfA*) secreted >100-fold more immunogen in broth culture than wild-type r-Listeria or r-Listeria ΔactA and elicited much greate ... Full text Link to item Cite

Host genetic determinants of T cell responses to the MRKAd5 HIV-1 gag/pol/nef vaccine in the step trial.

Journal Article J Infect Dis · March 15, 2011 Understanding how human genetic variation impacts individual response to immunogens is fundamental for rational vaccine development. To explore host mechanisms involved in cellular immune responses to the MRKAd5 human immunodeficiency virus type 1 (HIV-1) ... Full text Link to item Cite

Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.

Journal Article AIDS · February 20, 2011 OBJECTIVE: To date, CCR5 variants remain the only human genetic factors to be confirmed to impact HIV-1 acquisition. However, protective CCR5 variants are largely absent in African populations, in which sporadic resistance to HIV-1 infection is still unexp ... Full text Link to item Cite

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

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

Nonneutralizing HIV-1 gp41 envelope cluster II human monoclonal antibodies show polyreactivity for binding to phospholipids and protein autoantigens.

Journal Article J Virol · February 2011 HIV-1 gp41 envelope antibodies, which are frequently induced in HIV-1-infected individuals, are predominantly nonneutralizing. The rare and difficult-to-induce neutralizing antibodies (2F5 and 4E10) that target gp41 membrane-proximal epitopes (MPER) are po ... Full text Link to item Cite

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

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

Identification of amino acid substitutions associated with neutralization phenotype in the human immunodeficiency virus type-1 subtype C gp120.

Journal Article Virology · January 20, 2011 Neutralizing antibodies (Nabs) are thought to play an important role in prevention and control of HIV-1 infection and should be targeted by an AIDS vaccine. It is critical to understand how HIV-1 induces Nabs by analyzing viral sequences in both tested vir ... Full text Link to item Cite

Serendipity and Stamina: Staying the course

Chapter · January 1, 2011 During my career as a physician-scientist and my time as a mentor to young physician-scientists, I have been impressed that for success, one needs intellectual curiosity, good mentoring throughout one's career, the opportunity to work on important problems ... Full text Cite

Flow cytometry sorting of recombinant mycobacterial species yields bacterial clones with enhanced insert expression.

Journal Article Clin Vaccine Immunol · January 2011 Recombinant mycobacteria hold promise as vectors for delivery of HIV-1 and other pathogen antigen inserts for inducing systemic and mucosal immune responses. In general, the immunogenicity of the recombinant mycobacterial insert is proportional to the leve ... Full text Link to item Cite

A signature in HIV-1 envelope leader peptide associated with transition from acute to chronic infection impacts envelope processing and infectivity.

Journal Article PLoS One · 2011 Mucosal transmission of the human immunodeficiency virus (HIV) results in a bottleneck in viral genetic diversity. Gnanakaran and colleagues used a computational strategy to identify signature amino acids at particular positions in Envelope that were assoc ... Full text Link to item Cite

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

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

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

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

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

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

Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.

Journal Article PLoS One · 2011 BACKGROUND: Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HI ... Full text Link to item Cite

Characterization of glycosylation profiles of HIV-1 transmitted/founder envelopes by mass spectrometry

Journal Article Journal of Virology · 2011 The analysis of HIV-1 envelope carbohydrates is critical to understanding their roles in HIV-1 transmission as well as in binding of envelope to HIV-1 antibodies. However, direct analysis of protein glycosylation by glycopeptide-based mass mapping approach ... Full text Cite

Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane-proximal external region.

Journal Article Nat Struct Mol Biol · December 2010 The monoclonal antibody 13H11 shares part of its epitope in the HIV-1 gp41 membrane-proximal external region (MPER) with the rare, broadly neutralizing human antibody 2F5. Although 13H11 partially cross-blocked 2F5 binding, 13H11 is non-neutralizing and do ... Full text Link to item Cite

Induction of immunity to human immunodeficiency virus type-1 by vaccination.

Journal Article Immunity · October 29, 2010 Recent findings have brought optimism that development of a successful human immunodeficiency virus type-1 (HIV-1) vaccine lies within reach. Studies of early events in HIV-1 infection have revealed when and where HIV-1 is potentially vulnerable to vaccine ... Full text Link to item Cite

Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies.

Journal Article PLoS Comput Biol · October 7, 2010 A steady increase in knowledge of the molecular and antigenic structure of the gp120 and gp41 HIV-1 envelope glycoproteins (Env) is yielding important new insights for vaccine design, but it has been difficult to translate this information to an immunogen ... Full text Open Access Link to item Cite

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

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

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

Evolution of the Same HIV-1 Transmitted/Founder Virus in Two Hosts

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

The characterization of twenty sequenced human genomes.

Journal Article PLoS Genet · September 9, 2010 We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and te ... Full text Open Access 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

Anti-Ebola MAb 17A3 reacts with bovine and human alpha-2-macroglobulin proteins.

Journal Article J Virol Methods · September 2010 Monoclonal antibodies (MAbs) were developed against soluble Ebola virus (EBOV) envelope glycoprotein (GP) for the study of the diversity of EBOV envelope and development of diagnostic reagents. Of the three anti-EBOV GP mouse MAbs produced, MAb 15H10 recog ... 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

Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing.

Journal Article PLoS One · August 20, 2010 We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from regions targeted by CD8+ T lymphocytes from longitudinal samples from three acutely infected subjects, and modeled viral evolution during the critical first weeks of infectio ... Full text Open Access Link to item Cite

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

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

Contributions of Mamu-A*01 status and TRIM5 allele expression, but not CCL3L copy number variation, to the control of SIVmac251 replication in Indian-origin rhesus monkeys.

Journal Article PLoS Genet · June 24, 2010 CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral loa ... Full text Open Access Link to item Cite

Wide variation in the multiplicity of HIV-1 infection among injection drug users.

Journal Article J Virol · June 2010 Recent studies indicate that sexual transmission of human immunodeficiency virus type 1 (HIV-1) generally results from productive infection by only one virus, a finding attributable to the mucosal barrier. Surprisingly, a recent study of injection drug use ... Full text Link to item Cite

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.

Journal Article PLoS Pathog · May 13, 2010 Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution ha ... Full text Open Access Link to item Cite

Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection.

Journal Article PLoS Pathog · May 6, 2010 The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages an ... Full text Open Access Link to item Cite

HIV-1 autoreactive antibodies: are they good or bad for HIV-1 prevention?

Journal Article Nat Struct Mol Biol · May 2010 A new crystal structure of an anti–HIV-1 envelope antibody bound to an envelope–receptor complex shows the antibody binding both the HIV-1 envelope and the CD4 receptor, raising the question of what the role of antibody autoreactivity in host responses to ... Full text Link to item Cite

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

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

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

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

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

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

Stromal cell independent B cell development in vitro: generation and recovery of autoreactive clones.

Journal Article J Immunol Methods · March 31, 2010 We describe and characterize a stromal cell independent culture system that efficiently supports pro-B cell to IgM+ B cell development with near normal levels of IgH and Igkappa diversity. Pro-B cells present in non-adherent bone marrow cells proliferate i ... 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 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

Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys.

Journal Article Nat Med · March 2010 An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses. It must generate CD8+ T lymphocytes that control HIV replication and CD4+ T lymphocytes that provide help for the generation and maintenance of both cellular ... Full text Link to item Cite

Differential inhibition of human immunodeficiency virus type 1 in peripheral blood mononuclear cells and TZM-bl cells by endotoxin-mediated chemokine and gamma interferon production.

Journal Article AIDS Res Hum Retroviruses · March 2010 Bacterial lipopolysaccharide (endotoxin) is a frequent contaminant of biological specimens and is also known to be a potent inducer of beta-chemokines and other soluble factors that inhibit HIV-1 infection in vitro. Though lipopolysaccharide (LPS) has been ... Full text Open Access Link to item Cite

Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins.

Journal Article Viruses · February 2010 Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on stru ... Full text Link to item Cite

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

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

Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance.

Journal Article Proc Natl Acad Sci U S A · January 5, 2010 We previously reported that some of the rare broadly reactive, HIV-1 neutralizing antibodies are polyreactive, leading to the hypothesis that induction of these types of neutralizing antibody may be limited by immunologic tolerance. However, the notion tha ... Full text Link to item Cite

A polymorphism in the HCP5 gene associated with HLA-B*5701 does not restrict HIV-1 in vitro.

Journal Article AIDS · January 2, 2010 A single-nucleotide polymorphism (rs2395029) in the HCP5 gene associated with HLA-B*5701 is correlated with lower HIV-1 viral set point. The two allelic forms of coding region were ectopically expressed in TZM-bl cells for an effect on HIV-1 replication. N ... Full text Link to item Cite

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

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

HIV-Selectest enzyme immunoassay and rapid test: ability to detect seroconversion following HIV-1 infection.

Journal Article J Clin Microbiol · January 2010 HIV-Selectest is a serodiagnostic enzyme immunoassay (EIA), containing p6 and gp41 peptides, designed to differentiate between vaccine-induced antibodies and true infections. A rapid test version of the HIV-Selectest was developed. Both assays detected HIV ... Full text Link to item Cite

Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1.

Journal Article MAbs · 2010 Several human monoclonal antibodies (hmAbs) exhibit relatively potent and broad neutralizing activity against HIV-1, but there has not been much success in using them as potential therapeutics. We have previously hypothesized and demonstrated that small en ... Full text Open Access Link to item Cite

Contributions of Mamu-A*01 status and TRIM5 allele expression, but not CCL3L copy number variation, to the control of SIVmac251 replication in Indian-origin rhesus monkeys.

Journal Article PLoS genetics · 2010 CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral loa ... Full text Open Access Cite

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.

Journal Article PLoS pathogens · 2010 Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution ha ... Full text Cite

Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection.

Journal Article PLoS pathogens · 2010 The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages an ... Cite

Common genetic variation and the control of HIV-1 in humans.

Journal Article PLoS Genet · December 2009 To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the ... Full text Open Access Link to item Cite

Role of HIV membrane in neutralization by two broadly neutralizing antibodies.

Journal Article Proc Natl Acad Sci U S A · December 1, 2009 Induction of effective antibody responses against HIV-1 infection remains an elusive goal for vaccine development. Progress may require in-depth understanding of the molecular mechanisms of neutralization by monoclonal antibodies. We have analyzed the mole ... Full text Link to item Cite

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

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

P20-08. Glycosylation: An important factor in Env diversity

Journal Article Retrovirology · October 22, 2009 Full text Cite

Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region.

Journal Article PLoS One · October 6, 2009 The membrane proximal external region (MPER) of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is w ... Full text Link to item Cite

CCL3L1 and HIV/AIDS susceptibility.

Journal Article Nat Med · October 2009 Full text Link to item Cite

Stable docking of neutralizing human immunodeficiency virus type 1 gp41 membrane-proximal external region monoclonal antibodies 2F5 and 4E10 is dependent on the membrane immersion depth of their epitope regions.

Journal Article J Virol · October 2009 The binding of neutralizing antibodies 2F5 and 4E10 to human immunodeficiency virus type 1 (HIV-1) gp41 involves both the viral membrane and gp41 membrane proximal external region (MPER) epitopes. In this study, we have used several biophysical tools to ex ... Full text Link to item Cite

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

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

Glycosylation site-specific analysis of clade C HIV-1 envelope proteins.

Journal Article J Proteome Res · September 2009 The extensive glycosylation of HIV-1 envelope proteins (Envs), gp120/gp41, is known to play an important role in evasion of host immune response by masking key neutralization epitopes and presenting the Env glycosylation as "self" to the host immune system ... Full text Link to item Cite

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

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

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

Utilization of immunoglobulin G Fc receptors by human immunodeficiency virus type 1: a specific role for antibodies against the membrane-proximal external region of gp41.

Journal Article J Virol · August 2009 Receptors (FcgammaRs) for the constant region of immunoglobulin G (IgG) are an important link between humoral immunity and cellular immunity. To help define the role of FcgammaRs in determining the fate of human immunodeficiency virus type 1 (HIV-1) immune ... Full text Link to item Cite

Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates.

Journal Article Vaccine · July 23, 2009 Tuberculosis (TB) remains a global health burden for which safe vaccines are needed. BCG has limitations as a TB vaccine so we have focused on live attenuated Mycobacterium tuberculosis mutants as vaccine candidates. Prior to human studies, however, it is ... 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

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection.

Journal Article J Exp Med · June 8, 2009 Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 ac ... Full text Link to item Cite

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

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

Recombinant Mycobacterium bovis BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific T-cell responses.

Journal Article J Virol · June 2009 While mycobacteria have been proposed as vaccine vectors because of their persistence and safety, little has been done systematically to optimize their immunogenicity in nonhuman primates. We successfully generated recombinant Mycobacterium bovis BCG (rBCG ... Full text Link to item Cite

High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies.

Journal Article J Virol Methods · June 2009 Defining human B cell repertoires to viral pathogens is critical for design of vaccines that induce broadly protective antibodies to infections such as HIV-1 and influenza. Single B cell sorting and cloning of immunoglobulin (Ig) heavy- and light-chain var ... 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

Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1.

Journal Article J Exp Med · May 11, 2009 We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immun ... Full text Link to item Cite

The Duffy antigen receptor for chemokines null promoter variant does not influence HIV-1 acquisition or disease progression.

Journal Article Cell Host Microbe · May 8, 2009 Ma’am – We read with great interest the article by He et al. [2008] describing the effects on HIV acquisition and disease progression of a single-nucleotide polymorphism (SNP, rs2814778, -46T→C) that disrupts the promoter region of the Duffy antigen recept ... Full text Link to item Cite

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

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

Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants.

Journal Article J Virol · April 2009 Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a populatio ... Full text Link to item Cite

A critical role for CD8 T cells in a nonhuman primate model of tuberculosis.

Journal Article PLoS Pathog · April 2009 The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell-mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of impo ... 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

Expanded breadth of the T-cell response to mosaic human immunodeficiency virus type 1 envelope DNA vaccination.

Journal Article J Virol · March 2009 An effective AIDS vaccine must control highly diverse circulating strains of human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic ap ... Full text Link to item Cite

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

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

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

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

Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1alpha, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-beta, TIM1, and TLR2 but low antigen-specific cellular responses.

Journal Article J Infect Dis · November 15, 2008 The immune mechanisms by which early host-mycobacterium interaction leads to the development of severe tuberculosis (TB) remain poorly characterized in humans. Here, we demonstrate that severe TB in juvenile rhesus monkeys down-regulated many genes in the ... Full text Link to item Cite

Comparison of multiple vaccine vectors in a single heterologous prime-boost trial.

Journal Article Vaccine · November 11, 2008 The prevention of infectious disease via prophylactic immunization is a mainstay of global public health efforts. Vaccine design would be facilitated by a better understanding of the type and durability of immune responses generated by different vaccine ve ... Full text Link to item Cite

Antigen-specific B cell detection reagents: use and quality control.

Journal Article Cytometry A · November 2008 Tests for immunoglobulin reactivity with specific antigens are some of the oldest and most used assays in immunology. With efforts to understand B cell development, B cell dysregulation in autoimmunity, and to generate B cell vaccines for infectious agents ... Full text Link to item Cite

HIV-1 Immune Complexes are part of the Initial B cell Response in Acute HIV-1 infection

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

Comparison of HPLC/ESI-FTICR MS versus MALDI-TOF/TOF MS for glycopeptide analysis of a highly glycosylated HIV envelope glycoprotein.

Journal Article J Am Soc Mass Spectrom · August 2008 Defining the structures and locations of the glycans attached on secreted proteins and virus envelope proteins is important in understanding how glycosylation affects their biological properties. Glycopeptide mass spectrometry (MS)-based analysis is a very ... Full text Link to item Cite

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

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

A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys.

Journal Article Proc Natl Acad Sci U S A · July 29, 2008 One of the major challenges that must be met in developing an HIV-1 vaccine is devising a strategy to generate cellular immunity with sufficient breadth to deal with the extraordinary genetic diversity of the virus. Amino acids in the envelopes of viruses ... Full text Link to item Cite

Critical issues in mucosal immunity for HIV-1 vaccine development.

Journal Article J Allergy Clin Immunol · July 2008 Development of a safe and effective vaccine for HIV-1 infection is a critical global priority. However, the nature of host-virus interactions that lead to early immunosuppression and CD4 depletion, HIV-1 diversity, and the inability of the immune system to ... Full text Link to item Cite

Cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody that recognizes a novel conformational epitope on gp41 and lacks reactivity against self-antigens.

Journal Article J Virol · July 2008 Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear ep ... Full text Link to item Cite

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

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

Murine CD7 shares antigenic cross-reactivity with HSP-60.

Journal Article Hybridoma (Larchmt) · April 2008 Human (h) CD7 is a 40 kDa single chain Ig superfamily molecule that is expressed on thymocytes, a major subunit of peripheral T cells, and most natural killer cells. Ligands for hCD7 include the epithelial cell-produced molecule, K-12, and galectin. Mice d ... Full text Link to item Cite

Glycosylation site-specific analysis of HIV envelope proteins (JR-FL and CON-S) reveals major differences in glycosylation site occupancy, glycoform profiles, and antigenic epitopes' accessibility.

Journal Article J Proteome Res · April 2008 The HIV-1 envelope (Env) is a key determinant in mediating viral entry and fusion to host cells and is a major target for HIV vaccine development. While Env is typically about 50% glycan by mass, glycosylation sites are known to evolve, with some glycosyla ... Full text Link to item Cite

Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing.

Journal Article J Virol · April 2008 Accurate identification of the transmitted virus and sequences evolving from it could be instrumental in elucidating the transmission of human immunodeficiency virus type 1 (HIV-1) and in developing vaccines, drugs, or microbicides to prevent infection. He ... Full text Link to item Cite

Improving defences at the portal of HIV entry: mucosal and innate immunity.

Journal Article PLoS Med · April 1, 2008 The authors discuss the key scientific issues in mucosal and innate immunity related to immune protection against HIV infection. ... Full text Link to item Cite

HIV-1 hides an Achilles' heel in virion lipids.

Journal Article Immunity · January 2008 In this issue, Sun et al. (2008) model the interface between a neutralizing antibody and HIV-1 glycoprotein 41 (gp41) envelope peptide in lipids. This model could help overcome a roadblock in HIV-1 vaccine development. ... Full text Link to item Cite

Immune distribution and localization of phosphoantigen-specific Vgamma2Vdelta2 T cells in lymphoid and nonlymphoid tissues in Mycobacterium tuberculosis infection.

Journal Article Infect Immun · January 2008 Little is known about the immune distribution and localization of antigen-specific T cells in mucosal interfaces of tissues/organs during infection of humans. In this study, we made use of a macaque model of Mycobacterium tuberculosis infection to assess p ... Full text Link to item Cite

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

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

Centralized HIV-1 envelope immunogens and neutralizing antibodies.

Journal Article Curr HIV Res · November 2007 Centralized HIV-1 genes (consensus, most recent common ancestor and center of the tree) have recently been explored for induction of broadly reactive immune responses to overcome the extraordinary genetic diversity among HIV-1 strains. Although all of thes ... Full text Link to item Cite

In vitro and in vivo characterization of anthrax anti-protective antigen and anti-lethal factor monoclonal antibodies after passive transfer in a mouse lethal toxin challenge model to define correlates of immunity.

Journal Article Infect Immun · November 2007 Passive transfer of antibody may be useful for preexposure prophylaxis against biological agents used as weapons of terror, such as Bacillus anthracis. Studies were performed to evaluate the ability of anthrax antiprotective antigen (anti-PA) and antiletha ... Full text Link to item Cite

Incorporation of high levels of chimeric human immunodeficiency virus envelope glycoproteins into virus-like particles.

Journal Article J Virol · October 2007 The human immunodeficiency virus (HIV) envelope (Env) protein is incorporated into HIV virions or virus-like particles (VLPs) at very low levels compared to the glycoproteins of most other enveloped viruses. To test factors that influence HIV Env particle ... Full text Link to item Cite

Human T cell reconstitution in DiGeorge syndrome and HIV-1 infection.

Journal Article Semin Immunol · October 2007 The thymus is essential for proper development and maintenance of a broad T cell repertoire capable of recognizing a wide-range of foreign antigens. Recent advances in multicolor flow cytometry, non-invasive imaging techniques, and molecular assessments of ... Full text Link to item Cite

A whole-genome association study of major determinants for host control of HIV-1.

Journal Article Science · August 17, 2007 Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly ... Full text Link to item Cite

Recombinant Mycobacterium bovis bacillus Calmette-Guerin elicits human immunodeficiency virus type 1 envelope-specific T lymphocytes at mucosal sites.

Journal Article Clin Vaccine Immunol · July 2007 A successful vaccine vector for human immunodeficiency virus type 1 (HIV-1) should induce anti-HIV-1 T-cell immune responses at mucosal sites. We have constructed recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing an HIV-1 group M c ... Full text Link to item Cite

High throughput functional analysis of HIV-1 env genes without cloning.

Journal Article J Virol Methods · July 2007 Functional human immunodeficiency virus type 1 (HIV-1) env genes have been widely used for vaccine design, neutralization assays, and pathogenesis studies. However, obtaining bona fide functional env clones is a time consuming and labor intensive process. ... Full text Link to item Cite

The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes.

Journal Article J Immunol · April 1, 2007 Two neutralizing human mAbs, 2F5 and 4E10, that react with the HIV-1 envelope gp41 membrane proximal region are also polyspecific autoantibodies that bind to anionic phospholipids. To determine the autoantibody nature of these Abs, we have compared their r ... Full text Link to item Cite

Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins.

Journal Article Virology · March 30, 2007 "Centralized" (ancestral and consensus) HIV-1 envelope immunogens induce broadly cross-reactive T cell responses in laboratory animals; however, their potential to elicit cross-reactive neutralizing antibodies has not been fully explored. Here, we report t ... Full text Link to item Cite

Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis.

Journal Article J Virol · January 2007 The most promising vaccine strategies for the induction of cytotoxic-T-lymphocyte responses have been heterologous prime/boost regimens employing a plasmid DNA prime and a live recombinant-vector boost. The priming immunogen in these regimens must elicit a ... Full text Link to item Cite

Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants.

Journal Article Nat Med · January 2007 HIV-1/AIDS vaccines must address the extreme diversity of HIV-1. We have designed new polyvalent vaccine antigens comprised of sets of 'mosaic' proteins, assembled from fragments of natural sequences via a computational optimization method. Mosaic proteins ... Full text Link to item Cite

Generation of mucosal anti-human immunodeficiency virus type 1 T-cell responses by recombinant Mycobacterium smegmatis.

Journal Article Clin Vaccine Immunol · November 2006 A successful vaccine vector for human immunodeficiency virus type 1 (HIV-1) should induce anti-HIV-1 immune responses at mucosal sites. We have generated recombinant Mycobacterium smegmatis vectors that express the HIV-1 group M consensus envelope protein ... Full text Link to item Cite

Detection of Ebola virus envelope using monoclonal and polyclonal antibodies in ELISA, surface plasmon resonance and a quartz crystal microbalance immunosensor.

Journal Article J Virol Methods · November 2006 Ebola virus (EBOV) Zaire, Sudan, as well as Ivory Coast are virulent human EBOV species. Both polyclonal and monoclonal antibodies (MAbs) were developed against soluble EBOV envelope glycoprotein (GP) for the study of EBOV envelope diversity and developmen ... Full text Link to item Cite

A group M consensus envelope glycoprotein induces antibodies that neutralize subsets of subtype B and C HIV-1 primary viruses.

Journal Article Virology · September 30, 2006 HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a ce ... Full text Link to item Cite

Ancestral and consensus envelope immunogens for HIV-1 subtype C.

Journal Article Virology · September 1, 2006 Immunogens based on "centralized" (ancestral or consensus) HIV-1 sequences minimize the genetic distance between vaccine strains and contemporary viruses and should thus elicit immune responses that recognize a broader spectrum of viral variants. However, ... Full text Link to item Cite

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates.

Journal Article Expert Rev Vaccines · August 2006 Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and com ... Full text Link to item Cite

Leptin selectively augments thymopoiesis in leptin deficiency and lipopolysaccharide-induced thymic atrophy.

Journal Article J Immunol · July 1, 2006 The thymus is a lymphoid organ that selects T cells for release to the peripheral immune system. Unfortunately, thymopoiesis is highly susceptible to damage by physiologic stressors and can contribute to immune deficiencies that occur in a variety of clini ... Full text Link to item Cite

Cross-subtype T-cell immune responses induced by a human immunodeficiency virus type 1 group m consensus env immunogen.

Journal Article J Virol · July 2006 The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic group M consensus env gene (CON6) for induction of cross-subtype immune resp ... Full text Link to item Cite

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates.

Journal Article Expert Rev Vaccines · June 2006 Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and com ... Full text Link to item Cite

Analysis of HIV-1 subtype B third variable region peptide motifs for induction of neutralizing antibodies against HIV-1 primary isolates.

Journal Article Virology · February 5, 2006 The HIV-1 gp120 V3 loop is a potent inducer of neutralizing antibodies for T cell line adapted-HIV-1, but less so for primary isolates. We hypothesized that peptides representative of the diversity of natural HIV-1 V3 loop variants might capture elements o ... Full text Link to item Cite

Generation of CD8+ T-cell responses by a recombinant nonpathogenic Mycobacterium smegmatis vaccine vector expressing human immunodeficiency virus type 1 Env.

Journal Article J Virol · February 2006 Because the vaccine vectors currently being evaluated in human populations all have significant limitations in their immunogenicity, novel vaccine strategies are needed for the elicitation of cell-mediated immunity. The nonpathogenic, rapidly growing mycob ... Full text Link to item Cite

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

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

Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies.

Journal Article Science · June 24, 2005 The design of a human immunodeficiency virus-1 (HIV-1) immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human monoclonal antibodies (mAbs) exist that broadly neutralize HIV-1, HI ... Full text Link to item Cite

Expression of the CD7 ligand K-12 in human thymic epithelial cells: regulation by IFN-gamma.

Journal Article J Clin Immunol · January 2005 CD7 is an immunoglobulin superfamily molecule expressed on T, NK, and pre-B lymphocytes. Previous studies have demonstrated a role for CD7 in T- and NK-cell activation and cytokine production. Recently, an epithelial cell secreted protein, K12, was identif ... Full text Link to item Cite

Antibody polyspecificity and neutralization of HIV-1: a hypothesis.

Journal Article Hum Antibodies · 2005 HIV-1 has evolved many ways to evade protective host immune responses, thus creating a number of problems for HIV vaccine developers. In particular, durable, broadly specific neutralizing antibodies to HIV-1 have proved difficult to induce with current HIV ... Link to item Cite

Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type 1 group m consensus envelope glycoprotein.

Journal Article J Virol · January 2005 Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group ... Full text Link to item Cite

Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies.

Journal Article AIDS Res Hum Retroviruses · January 2005 Designing an immunogen for effective neutralizing antibody induction against diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) is a high priority for HIV-1 vaccine development. Soluble gp120 envelope (Env) glycoprotein subunit vaccine ... Full text Link to item Cite

Gender differences in human immunodeficiency virus type 1-specific CD8 responses in the reproductive tract and colon following nasal peptide priming and modified vaccinia virus Ankara boosting.

Journal Article J Virol · December 2004 Induction of mucosal anti-human immunodeficiency virus type 1 (HIV-1) T-cell responses in males and females will be important for the development of a successful HIV-1 vaccine. An HIV-1 envelope peptide, DNA plasmid, and recombinant modified vaccinia virus ... Full text Link to item Cite

A comparative evaluation of nasal and parenteral vaccine adjuvants to elicit systemic and mucosal HIV-1 peptide-specific humoral immune responses in cynomolgus macaques.

Journal Article Vaccine · September 9, 2004 Cynomolgus macaques were immunized by either the intramuscular (i.m.) or intranasal (i.n.) route with a HIV-1 peptide-based immunogen (C4-V3 89.6P) alone, or formulated with novel adjuvants to evaluate the ability of the adjuvants to augment peptide-specif ... Full text Link to item Cite

An inducible HIV type 1 gp41 HR-2 peptide-binding site on HIV type 1 envelope gp120.

Journal Article AIDS Res Hum Retroviruses · August 2004 Synthetic peptides of sequences within the HIV-1 gp41 heptad repeat-regions (HR-1 and HR-2) can effectively inhibit cell fusion and viral entry. DP178 (T-20), an HR-2 peptide, acts by inhibiting the association between HR-1 and HR-2, thereby interfering wi ... Full text Link to item Cite

Centralized immunogens as a vaccine strategy to overcome HIV-1 diversity.

Journal Article Expert Rev Vaccines · August 2004 Genetic variation of HIV-1 represents a major obstacle for AIDS vaccine development. With the amino acid sequence divergence as high as 30% in envelopes between different subtypes among HIV-1 group M viruses, it is unlikely that cross-subtype protection wi ... Full text Link to item Cite

Immunogenicity of constrained monoclonal antibody A32-human immunodeficiency virus (HIV) Env gp120 complexes compared to that of recombinant HIV type 1 gp120 envelope glycoproteins.

Journal Article J Virol · May 2004 One strategy for the generation of broadly reactive neutralizing antibodies (NA) against human immunodeficiency virus type 1 (HIV-1) primary isolates is to use immunogens that have constrained HIV-1 envelope gp120 conformations reflective of triggered enve ... Full text Link to item Cite

The challenges of an HIV vaccine enterprise.

Journal Article Science · February 27, 2004 Full text Link to item Cite

The challenges of an HIV vaccine enterprise - Response

Journal Article SCIENCE · February 27, 2004 Link to item Cite

CD7 and CD28 are required for murine CD4+CD25+ regulatory T cell homeostasis and prevention of thyroiditis.

Journal Article J Immunol · January 15, 2004 CD7 and CD28 are T cell Ig superfamily molecules that share common signaling mechanisms. To determine roles CD7 and CD28 might play in peripheral lymphocyte development and function, we have generated CD7/CD28-double-deficient mice. CD7- and CD28-single-de ... Full text Link to item Cite

Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients.

Journal Article Blood · August 1, 2003 Complete DiGeorge syndrome is a fatal condition in which infants have no detectable thymus function. The optimal treatment for the immune deficiency of complete DiGeorge syndrome has not been determined. Safety and efficacy of thymus transplantation were e ... Full text Link to item Cite

Medicine. The need for a global HIV vaccine enterprise.

Journal Article Science · June 27, 2003 A new collaborative model of research is needed to increase resources, to prioritize the R (ii) to increase the pace, reduce the overlap, and more systematically explore the elements of and delivery systems for vaccines; (iii) to use common standards for t ... Full text Link to item Cite

Leukemia inhibitory factor is a mediator of Escherichia coli lipopolysaccharide-induced acute thymic atrophy.

Journal Article Eur J Immunol · November 2002 Septic shock in animals and humans is associated with thymic atrophy and generalized lymphocyte apoptosis that impairs T cell responses. Injection of animals with E. coli lipopolysaccharide (LPS) mimics bacterial sepsis-induced thymic atrophy. Leukemia inh ... Full text Link to item Cite

Diversity considerations in HIV-1 vaccine selection.

Journal Article Science · June 28, 2002 Globally, human immunodeficiency virus-type 1 (HIV-1) is extraordinarily variable, and this diversity poses a major obstacle to AIDS vaccine development. Currently, candidate vaccines are derived from isolates, with the hope that they will be sufficiently ... Full text Link to item Cite

Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF.

Journal Article Vaccine · May 22, 2002 Critical to the success of HIV-1 subunit vaccines is the development of strategies to augment vaccine immunogenicity. Successful adjuvants must not only improve immunogenicity above current adjuvant levels, but must also decrease the dose of immunogen requ ... Full text Link to item Cite

T cell receptor excision circle assessment of thymopoiesis in aging mice.

Journal Article Mol Immunol · March 2002 Signal joint T cell receptor delta (TCRD) excision circles (TRECs) are episomal DNA circles generated by the DNA recombination process that is used by T lymphocytes to produce antigen-specific alpha/beta T cell receptors. Measurement of TRECs in thymocytes ... Full text Link to item Cite

Immune reconstitution in patients with HIV infection.

Journal Article Annu Rev Med · 2002 The peripheral T cell pool is damaged by HIV-1 infection and can be regenerated by production of new T lymphocytes either from the thymus or from proliferation of post-thymic T cells. A critical question for AIDS patients is whether treatment with antiretr ... Full text Link to item Cite

A comparison of murine T-cell-depleted adult bone marrow and full-term fetal blood cells in hematopoietic engraftment and immune reconstitution.

Journal Article Blood · January 1, 2002 Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. A major area of concern for the use of cord blood transplantation is the delay in myeloid and lymphoid recovery. To directly compare myeloid and lymphoid recovery usin ... Full text Link to item Cite

Cytokines as adjuvants for the induction of anti-human immunodeficiency virus peptide immunoglobulin G (IgG) and IgA antibodies in serum and mucosal secretions after nasal immunization.

Journal Article J Virol · January 2002 Safe and potent new adjuvants are needed for vaccines that are administered to mucosal surfaces. This study was performed to determine if interleukin-1alpha (IL-1alpha) combined with other proinflammatory cytokines provided mucosal adjuvant activity for in ... Full text Link to item Cite

Thymopoiesis in HIV-infected adults after highly active antiretroviral therapy.

Journal Article AIDS Res Hum Retroviruses · November 20, 2001 The thymus of HIV-seropositive patients can enlarge as CD4+ T cell counts increase on highly active anti-retroviral therapy (HAART). This may indicate development of new T cells or represent mature peripheral T cells recirculating to the thymus. To define ... Full text Link to item Cite

Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization.

Journal Article J Immunol · November 1, 2001 Cholera toxin (CT) is frequently used as an experimental adjuvant intranasally for the induction of systemic and mucosal immunity. However, CT is highly reactogenic and not approved for use in humans. To define the cytokine requirements for the nasal activ ... Full text Link to item Cite

The exon A (C77G) mutation is a common cause of abnormal CD45 splicing in humans.

Journal Article J Immunol · May 15, 2001 The leukocyte common (CD45) Ag is essential for normal T lymphocyte function and alternative splicing at the N terminus of the gene is associated with changes in T cell maturation and differentiation. Recently, a statistically significant association was r ... Full text Link to item Cite

Vaccine-elicited V3 loop-specific antibodies in rhesus monkeys and control of a simian-human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate envelope.

Journal Article J Virol · May 2001 Vaccine-elicited antibodies specific for the third hypervariable domain of the surface gp120 of human immunodeficiency virus type 1 (HIV-1) (V3 loop) were assessed for their contribution to protection against infection in the simian-human immunodeficiency ... Full text Link to item Cite

Effect of thymectomy on human peripheral blood T cell pools in myasthenia gravis.

Journal Article J Immunol · February 15, 2001 The human thymus is required for establishment of the T cell pool in fetal life, but postnatal thymectomy does not lead to immunodeficiency in humans. Because thymectomy in humans is performed for treatment of myasthenia gravis (MG), we have studied patien ... Full text Link to item Cite

Comparison of thymocyte development and cytokine production in CD7-deficient, CD28-deficient and CD7/CD28 double-deficient mice.

Journal Article Int Immunol · February 2001 CD7 and CD28 are Ig superfamily molecules expressed on thymocytes and mature T cells that share common signaling 0mechanisms and are co-mitogens for T cell activation. CD7-deficient mice are resistant to lipopolysaccharide (LPS)-induced shock syndrome, and ... Full text Link to item Cite

Towards a genomic-based diagnosis.

Journal Article Lancet · January 27, 2001 Full text Link to item Cite

T-Cell recovery in adults and children following umbilical cord blood transplantation.

Journal Article Biol Blood Marrow Transplant · 2001 T-cell reconstitution following allogeneic stem cell transplantation may involve thymic education of donor-derived precursors or peripheral expansion of mature T cells transferred in the graft. T cell-receptor excision circles (sjTRECs) are generated withi ... Full text Link to item Cite

Leukocyte homing to synovium.

Journal Article Curr Dir Autoimmun · 2001 Full text Link to item Cite

Activated T lymphocytes regulate hyaluronan binding to monocyte CD44 via production of IL-2 and IFN-gamma.

Journal Article J Immunol · January 1, 2001 Interactions of the cell surface proteoglycan CD44 with the extracellular matrix glycosaminoglycan hyaluronan (HA) are important during inflammatory immune responses. Our previous studies indicated that monocyte HA binding could be induced by TNF-alpha. Mo ... Full text Link to item Cite

Cytokines and adhesion molecules in the pathogenesis of vasculitis.

Journal Article Curr Rheumatol Rep · October 2000 Upregulated adhesion molecule and cytokine expression on endothelial cells and infiltrating inflammatory cells occur in most vasculitis syndromes. These observations suggest that vasculitis is associated with pathologic activation of normal immune cell cyt ... Full text Link to item Cite

Linkage of the CCR5 Delta 32 mutation with a functional polymorphism of CD45RA.

Journal Article J Immunol · July 1, 2000 A 32-bp deletion in CCR5 (CCR5 Delta 32) confers to PBMC resistance to HIV-1 isolates that use CCR5 as a coreceptor. To study this mutation in T cell development, we have screened 571 human thymus tissues for the mutation. We identified 72 thymuses (12.6%) ... Full text Link to item Cite

Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency.

Journal Article N Engl J Med · May 4, 2000 BACKGROUND: Immune function can be restored in infants with severe combined immunodeficiency by transplantation of unfractionated bone marrow from HLA-identical donors or T-cell-depleted marrow stem cells from haploidentical donors, with whom there is a si ... Full text Link to item Cite

Effect of thymectomy on human peripheral T cell pools.

Journal Article FASEB JOURNAL · April 20, 2000 Link to item Cite

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

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

Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy.

Journal Article J Immunol · February 15, 2000 The roles that thymus cytokines might play in regulating thymic atrophy are not known. Reversing thymic atrophy is important for immune reconstitution in adults. We have studied cytokine mRNA steady-state levels in 45 normal human (aged 3 days to 78 years) ... Full text Link to item Cite

Cogan’s syndrome

Chapter · January 1, 2000 The hallmarks of Cogan’s syndrome (CS) are interstitial keratitis (IK) and vestibuloauditory dysfunction. The history of CS reflects a growing awareness of its potential for causing not only eye and ear disease, but also complex systemic manifestations. In ... Full text Cite

Induction of antibodies in guinea pigs and rhesus monkeys against the human immunodeficiency virus type 1 envelope: neutralization of nonpathogenic and pathogenic primary isolate simian/human immunodeficiency virus strains.

Journal Article J Virol · January 2000 We have compared the abilities of human immunodeficiency virus type 1 (HIV-1) envelope V3 peptides and recombinant gp120 to induce antibodies that neutralize simian/human immunodeficiency viruses (SHIVs). SHIV-89.6 is a nonpathogenic SHIV that expresses th ... Full text Link to item Cite

The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection.

Journal Article Annu Rev Immunol · 2000 The human thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants a ... Full text Link to item Cite

HIV vaccine development at Duke University Medical Center.

Journal Article Immunol Res · 2000 With the AIDS epidemic continuing to spread throughout the world, development of a safe, practical, and effective HIV vaccine is a national priority. HIV vaccine research efforts are currently targeted towards design of HIV immunogens that induce both cell ... Full text Link to item Cite

The human thymus during aging.

Journal Article Immunol Res · 2000 The human thymus is required for establishment of a normal T cell repertoire in fetal development, as children born without a thymus (DiGeorge Syndrome) lack thymus-derived (T) and T cell immunity. While the function of the thymus in children for productio ... Full text Link to item Cite

Transplantation of thymus tissue in complete DiGeorge syndrome.

Journal Article N Engl J Med · October 14, 1999 BACKGROUND: The DiGeorge syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge syndrome, patients have severely reduced T-cell function. METHODS: We treated five infants (age, one to four months) wit ... Full text Link to item Cite

Analysis of the human thymic perivascular space during aging.

Journal Article J Clin Invest · October 1999 The perivascular space (PVS) of human thymus increases in volume during aging as thymopoiesis declines. Understanding the composition of the PVS is therefore vital to understanding mechanisms of thymic atrophy. We have analyzed 87 normal and 31 myasthenia ... Full text Link to item Cite

TNFalpha and IL-4 regulation of hyaluronan binding to monocyte CD44 involves posttranslational modification of CD44.

Journal Article Cell Immunol · May 1, 1999 Our previous studies have identified TNFalpha as a positive regulator and IL-4 as a negative regulator of human monocyte CD44-HA binding. In order to determine the mechanisms of IL-4- and TNFalpha-mediated regulation of monocyte HA binding, we measured HA ... Full text Link to item Cite

Molecular analysis of ALCAM (CD166) mediated homophilic cell adhesion

Journal Article JOURNAL OF INVESTIGATIVE MEDICINE · April 1, 1999 Link to item Cite

Resistance of CD7-deficient mice to lipopolysaccharide-induced shock syndromes.

Journal Article J Exp Med · March 15, 1999 CD7 is an immunoglobulin superfamily molecule involved in T and natural killer (NK) cell activation and cytokine production. CD7-deficient animals develop normally but have antigen-specific defects in interferon (IFN)-gamma production and CD8(+) CTL genera ... Full text Link to item Cite

Thymic function, aging, and AIDS.

Journal Article Hosp Pract (1995) · March 15, 1999 For the first time, physicians are challenged by clinical states in which the T-cell pool is destroyed postnatally in large numbers of patients. One such state is AIDS; another is the immune damage of cancer chemotherapy. Accordingly, study of postnatal th ... Full text Link to item Cite

Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection.

Journal Article J Clin Invest · February 1999 A key question in understanding the status of the immune system in HIV-1 infection is whether the adult thymus contributes to reconstitution of peripheral T lymphocytes. We analyzed the thymus in adult patients who died of HIV-1 infection. In addition, we ... Full text Link to item Cite

Milestones for training safe doctors who are good doctors.

Journal Article Pharos Alpha Omega Alpha Honor Med Soc · 1999 Link to item Cite

Nuclear magnetic resonance analysis of solution conformations in C4-V3 hybrid peptides derived from human immunodeficiency virus (HIV) type 1 gp120: relation to specificity of peptide-induced anti-HIV neutralizing antibodies.

Journal Article J Virol · January 1999 Immunogenic peptides containing epitopes of the gp120 C4 and V3 regions from human immunodeficiency virus strains MN and EV91 have been studied by nuclear magnetic resonance and molecular modeling and used as immunogens in rhesus monkeys. The results, comb ... Full text Link to item Cite

Structure and function of the CD7 molecule.

Journal Article Crit Rev Immunol · 1999 CD7 is a single-domain Ig superfamily molecule expressed on human T and NK cells, as well as on cells in the early stages of T, B, and myeloid cell differentiation. CD7 is highly expressed on malignant immature T cells and is generally absent on malignant ... Link to item Cite

14G8 anti-LSP-1

Journal Article Hybridoma · January 1, 1999 Full text Cite

5E3 anti-LSP-1

Journal Article Hybridoma · January 1, 1999 Full text Cite

Changes in thymic function with age and during the treatment of HIV infection.

Journal Article Nature · December 17, 1998 The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens th ... Full text Link to item Cite

Developmental regulation of lymphocyte-specific protein 1 (LSP1) expression in thymus during human T-cell maturation.

Journal Article Hybridoma · December 1998 The lymphocyte specific protein 1 (LSP1) phosphoprotein is an F-actin binding molecule restricted to cells of hematopoietic origin in mice and humans. LSP1 is localized to the internal surface of the plasma membrane, the cytoplasm, and NP-40-insoluble acti ... Full text Link to item Cite

New surrogate markers for autoimmune disease activity.

Journal Article J Clin Invest · September 15, 1998 Full text Link to item Cite

Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative.

Journal Article AIDS · July 30, 1998 OBJECTIVE: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-he ... Full text Link to item Cite

Immunologic characterization of CD7-deficient mice.

Journal Article J Immunol · June 15, 1998 Human CD7 is an Ig superfamily molecule that is expressed on mature T and NK lymphocytes. Although in vitro studies have suggested a role for CD7 in lymphoid development and function, the exact function of CD7 in vivo has remained elusive. One patient has ... Link to item Cite

CD34+CD38-lin- cord blood cells develop into dendritic cells in human thymic stromal monolayers and thymic nodules.

Journal Article J Immunol · April 1, 1998 Thymic dendritic cells (DCs) appear to have distinct biologic and functional properties compared with DCs in other tissues. Currently, little is known about human thymic DCs because they have been difficult to isolate and culture in vitro. Here, we report ... Link to item Cite

The human thymus. A chimeric organ comprised of central and peripheral lymphoid components.

Journal Article Immunol Res · 1998 The human thymus is a lymphoepithelial organ in which T cells develop during fetal life. After maturation and selection in the fetal thymic microenvironment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and esta ... Full text Link to item Cite

The human thymus. A chimeric organ comprised of central and peripheral lymphoid components.

Journal Article Immunol Res · 1998 The human thymus is a lymphoepithelial organ in which T cells develop during fetal life. After maturation and selection in the fetal thymic microenvironment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and esta ... Full text Link to item Cite

Cytokine induction of the ability of human monocyte CD44 to bind hyaluronan is mediated primarily by TNF-alpha and is inhibited by IL-4 and IL-13.

Journal Article J Immunol · December 15, 1997 Ligation of CD44 by hyaluronan (HA) is a key proinflammatory event that regulates lymphocyte and monocyte adhesion and cytokine production. While most immune cells express CD44, few immune cells constitutively bind HA. We have previously shown that monocyt ... Link to item Cite

CD6-ligand interactions: a paradigm for SRCR domain function?

Journal Article Immunol Today · October 1997 The scavenger receptor cysteine-rich (SRCR) superfamily, which includes proteins expressed by leukocytes, can be subdivided into groups A and B. Group B contains the lymphocyte cell-surface receptor CD6. This article reviews recent progress in understandin ... Full text Link to item Cite

Identification of a synthetic peptide that mimics an HIV glycoprotein 120 envelope conformational determinant exposed following ligation of glycoprotein 120 by CD4.

Journal Article AIDS Res Hum Retroviruses · May 20, 1997 CD4 ligation of HIV envelope gp120 results in conformational changes in gp120 that lead to exposure of the gp41 fusogenic domain and fusion with the host cell membrane. One determinant at or near the CD4-binding site exposed on gp120 subsequent to CD4 bind ... Full text Link to item Cite

Normalization of the peripheral blood T cell receptor V beta repertoire after cultured postnatal human thymic transplantation in DiGeorge syndrome.

Journal Article J Clin Immunol · March 1997 Complete DiGeorge syndrome is an immunodeficiency disease characterized by thymic aplasia and the absence of functioning peripheral T cells. A patient with this syndrome was transplanted with cultured postnatal human thymic tissue. Within 5 weeks of transp ... Full text Link to item Cite

Immunotherapy for HIV.

Journal Article Lancet · February 8, 1997 Full text Link to item Cite

Immunotherapy for HIV

Journal Article The Lancet · February 1997 Full text Cite

Successful formation of a chimeric human thymus allograft following transplantation of cultured postnatal human thymus.

Journal Article J Immunol · January 15, 1997 Transplantation of cultured postnatal human thymus was performed in a patient with complete DiGeorge syndrome. Biopsy of the graft 3 mo after implantation revealed normal CD1+ thymocytes in thymic cortical epithelial regions and CD1- thymocytes in thymic m ... Link to item Cite

Arthritis syndromes associated with human T cell lymphotropic virus type I infection.

Journal Article Med Clin North Am · January 1997 Arthritis syndromes occur associated with HTLV-I infection both in the presence and in the absence of clinical ATL, and polyarthritis may be the presenting manifestation of HTLV-I-associated ATL. In both clinical settings, HTLV-I-infected T cells home to a ... Full text Link to item Cite

The human thymic microenvironment during organ culture.

Journal Article Clin Immunol Immunopathol · January 1997 Cultured human thymic tissue has been transplanted into many patients with T cell dysfunction; however, little is known about the effect of in vitro culture on thymic tissue. Human postnatal thymic organ cultures were established in vitro to study the grow ... Full text Link to item Cite

Mentoring physician-scientists: fear of the unknown and scientific opportunity.

Journal Article Pharos Alpha Omega Alpha Honor Med Soc · 1997 Link to item Cite

Advances in rheumatology - Preface

Journal Article MEDICAL CLINICS OF NORTH AMERICA · January 1, 1997 Link to item Cite

In vitro formation of the human thymic microenvironment: Similarity to SCID thymus.

Journal Article JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · January 1, 1997 Link to item Cite

New frontiers of immunotherapy for HIV.

Journal Article Lancet · December 7, 1996 Full text Link to item Cite

HIV vaccines: where we are and where we are going.

Journal Article Lancet · October 5, 1996 As the HIV-1 epidemic continues to spread world wide, the need for an effective vaccine remains urgent. Efforts to develop such a vaccine have been hampered by three main factors: (a) the extraordinary ability of the virus to mutate; (b) inability of most ... Full text Link to item Cite

Functional association of CD7 with phosphatidylinositol 3-kinase: interaction via a YEDM motif.

Journal Article Int Immunol · August 1996 Human CD7 is a 40 kDa protein expressed on thymocytes, early T, B, NK and myeloid lineage cells in bone marrow, and on mature T and NK cells. Previous studies suggested human CD7 may be involved in T and NK cell activation and/or adhesion, and that CD7-med ... Full text Link to item Cite

HIV quasispecies and resampling.

Journal Article Science · July 26, 1996 Full text Link to item Cite

HIV quasispecies and resampling - Response

Journal Article SCIENCE · July 26, 1996 Link to item Cite

A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency.

Journal Article Immunity · May 1996 Tristetraprolin (TTP) is a widely expressed potential transcription factor that contains two unusual CCCH zinc fingers and is encoded by the immediate-early response gene, Zfp-36. Mice made deficient in TTP by gene targeting appeared normal at birth, but s ... Full text Link to item Cite

Thymic transplantation for digeorge syndrome.

Journal Article FASEB JOURNAL · April 30, 1996 Link to item Cite

Conformational preferences of a chimeric peptide HIV-1 immunogen from the C4-V3 domains of gp120 envelope protein of HIV-1 CAN0A based on solution NMR: comparison to a related immunogenic peptide from HIV-1 RF.

Journal Article Biochemistry · April 23, 1996 A critical problem to overcome on HIV vaccine design is the variability among HIV strains. One strategy to solve this problem is the construction of multicomponent immunogens reflective of common HIV motifs. Currently, it is not known if these motifs shoul ... Full text Link to item Cite

Response: HIV Viral Load Assay.

Journal Article Science · February 23, 1996 Full text Link to item Cite

HIV viral load assay.

Journal Article Science · February 23, 1996 Link to item Cite

HIV viral load assay - Reply

Journal Article SCIENCE · February 23, 1996 Link to item Cite

In vitro culture of human peripheral blood monocytes induces hyaluronan binding and up-regulates monocyte variant CD44 isoform expression.

Journal Article J Immunol · February 15, 1996 CD44 is a cell surface proteoglycan homologous to cartilage link protein that serves as a receptor for hyaluronan (HA). CD44 isoforms include an unspliced 80- to 90-kDa standard form (CD44S) and isoforms derived from alternative splicing of nine CD44 varia ... Link to item Cite

Update on the issues of HIV vaccine development.

Journal Article Ann Med · February 1996 Major scientific obstacles blocking the development of a successful preventive HIV vaccine are the extraordinary variability of HIV, the lack of an exact animal model of HIV-induced AIDS, and the lack of understanding of the correlates of positive immunity ... Full text Link to item Cite

Toward an understanding of the correlates of protective immunity to HIV infection.

Journal Article Science · January 19, 1996 Considerable progress has been made recently in understanding the genetic, immunologic and virologic factors in human immunodeficiency virus (HIV)-infected individuals who either rapidly progress or do not progress to acquired immunodeficiency syndrome (AI ... Full text Link to item Cite

HIV-1 peptide immunogens as vaccine and immunotherapy candidates

Conference RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES · January 1, 1996 Link to item Cite

The mouse CD7 gene: identification of a new element common to the human CD7 and mouse Thy-1 promoters.

Journal Article Immunogenetics · 1996 Human CD7 (hCD7) is a 40 000 Mr member of the immunoglobulin gene superfamily that is expressed early in natural killer (NK) and T-lymphocyte development. CD7 is involved in lymphocyte activation, as ligation of CD7 activates NK and TCRgammadelta T lymphoc ... Link to item Cite

Regulated expression of activated leukocyte cell adhesion molecule, a ligand for cd6, in rheumatoid arthritis synovium

Journal Article Journal of Investigative Medicine · January 1, 1996 CD6, a 130 kDa glycoprotein expressed on the surface of T cells and a subset of B cells, is involved in TCR-mediated T cell activation and has been implicated in mediating autoreactive immune responses. We have recently identified a 100 kDa glycoprotein li ... Cite

Myotropic Th1 T helper cell lymphoma presenting as granulomatous inflammatory masses in synovium and muscle

Journal Article Journal of Investigative Medicine · January 1, 1996 Human T helper (Th) lymphocyte subsets can be differentiated by cytokine production; Thl cells produce inteferon-gamma and interleukin-2, while Th2 cells produce interleukin-4 and interleukin-5. Imbalance of Th subsets leads to disordered immunity and a my ... Cite

Initial characterization of cd7 deficient mice: evidence of a role for CD7 in regulation of thymocyte development

Journal Article Journal of Investigative Medicine · January 1, 1996 Human CD7 is a 40 kilodalton member of the immunoglobulin gene superfamily that is expressed early in natural killer and T lymphocyte development. Although CD7 involvement in lymphocyte activation has been suggested by numerous studies, the functional role ... Cite

Constitutive cytokine mRNA production in human post-natal thymus: RT-PCR analysis of cellular subsets.

Journal Article JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · January 1, 1996 Link to item Cite

Distribution of CD44 variant isoforms in human skin: differential expression in components of benign and malignant epithelia.

Journal Article J Cutan Pathol · December 1995 Expression of cell adhesion molecules regulates epithelial cell differentiation and organization of complex tissues such as skin. The CD44 family of adhesion molecules is generated by alternative splicing of up to 10 variant exons encoding inserts into the ... Full text Link to item Cite

Pathogenic mechanisms of vessel damage in vasculitis syndromes.

Journal Article Rheum Dis Clin North Am · November 1995 The pathogenesis of vasculitis syndromes is via a diverse array of mechanisms that disrupt vessel integrity and produce clinical signs and symptoms of tissue ischemia. In many patients with vasculitis, it is not possible to directly classify the syndrome a ... Link to item Cite

N-terminal and central regions of the human CD44 extracellular domain participate in cell surface hyaluronan binding.

Journal Article J Immunol · October 15, 1995 CD44 molecules are cell surface receptors for hyaluronan (HA). To define regions of the extracellular domain of CD44 that are important for HA binding, we have studied the ability of HA-blocking CD44 mAbs to bind to CD44 from a variety of sources. Five CD4 ... Link to item Cite

DEVELOPMENT OF T-CELL FUNCTION AFTER POSTNATAL THYMIC TRANSPLANTATION FOR DIGEORGE-SYNDROME

Journal Article AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 1995 Link to item Cite

Characterization of human CD7 transgenic mice.

Journal Article J Immunol · September 1, 1995 CD7 is a 40-kDa transmembrane glycoprotein member of the lg gene superfamily expressed on most peripheral blood T lymphocytes and NK cells. CD7 is also expressed on myeloid, NK, B, and T cell precursors during adult hematopoiesis. Because Thy-1 is absent i ... Link to item Cite

Role of adhesion molecules in the pathogenesis of rheumatoid arthritis.

Journal Article Rheum Dis Clin North Am · August 1995 The pathogenesis of rheumatoid arthritis centers on as yet unknown initiating events in the synovium that result in synovial vessel proliferation, and upregulation of endothelial cell ligands for leukocyte adhesion molecules. Ligation of adhesion molecules ... Link to item Cite

Cellular CD44S as a determinant of human immunodeficiency virus type 1 infection and cellular tropism.

Journal Article J Virol · July 1995 CD4 is the predominant cell membrane protein that binds human immunodeficiency virus type 1 (HIV-1) gp120 and facilitates HIV-1 infection, but other membrane-associated molecules may be involved in determining HIV-1 cellular infection. Our prior work had s ... Full text Link to item Cite

Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand.

Journal Article J Exp Med · June 1, 1995 Antibody-blocking studies have demonstrated the role of CD6 in thymocyte-thymic epithelial (TE) cell adhesion. Here we report that CD6 expressed by COS cells mediates adhesion to TE cells and that this interaction is specifically blocked with an anti-CD6 m ... Full text Link to item Cite

Inhibition of HIV type 1 infection of mononuclear phagocytes by anti-CD44 antibodies.

Journal Article AIDS Res Hum Retroviruses · May 1995 Cellular CD4 is the primary membrane molecule that binds HIV-1 through interaction with viral gp120. Membrane glycolipids and cell adhesion molecules have also been noted to be involved in the interaction of HIV-1 with cells and in syncytium formation in i ... Full text Link to item Cite

Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells.

Journal Article J Exp Med · April 1, 1995 CD6 is a 130-kD glycoprotein expressed on the surface of thymocytes and peripheral blood T cells that is involved in TCR-mediated T cell activation. In thymus, CD6 mediates interactions between thymocytes and thymic epithelial (TE) cells. In indirect immun ... Full text Link to item Cite

Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment.

Journal Article J Exp Med · April 1, 1995 To determine events that transpire during the earliest stages of human T cell development, we have studied fetal tissues before (7 wk), during (8.2 wk), and after (9.5 wk to birth) colonization of the fetal thymic rudiment with hematopoietic stem cells. Ca ... Full text Link to item Cite

Characterization of human thymic epithelial cell surface antigens: phenotypic similarity of thymic epithelial cells to epidermal keratinocytes.

Journal Article J Clin Immunol · March 1995 Cellular interactions between developing thymocytes and cells of the thymic microenvironment are necessary for maturation of thymocytes into mature T cells. While much is known about the molecules on developing T cells that mediate these interactions, litt ... Full text Link to item Cite

AD2, a human molecule involved in the interaction of T cells with epidermal keratinocytes and thymic epithelial cells.

Journal Article J Immunol · March 1, 1995 Interactions between T cells and epithelial cells of the thymus are essential for normal T cell development, and interactions between T cells and skin epidermal keratinocytes occur in the context of inflammatory skin diseases and cutaneous T cell malignanc ... Link to item Cite

Expression of CD44 molecules and CD44 ligands during human thymic fetal development: expression of CD44 isoforms is developmentally regulated.

Journal Article Int Immunol · February 1995 It has recently been recognized that CD44 comprises a large family of alternatively spliced forms. In the thymus, CD44 has been postulated to play an important role in immature T cell migration and maturation. In this paper, we have studied the expression ... Full text Link to item Cite

HIV type 1 V3 region primer-induced antibody suppression is overcome by administration of C4-V3 peptides as a polyvalent immunogen.

Journal Article AIDS Res Hum Retroviruses · February 1995 The extreme variability of HIV-1 immunogenic regions has hampered attempts to design immunogens capable of inducing broadly reactive neutralizing anti-HIV antibody responses. We have begun to study the immune responses generated to a polyvalent mixture of ... Full text Link to item Cite

Activation of interleukin 4- and interleukin 6-secreting cells by HIV-specific synthetic peptides.

Journal Article AIDS Res Hum Retroviruses · January 1995 Peptides were synthesized in which the type-specific determinant of the V3 loop region of gp120 (SP10) was expressed C terminal to a conserved T helper epitope (T1) on the same molecule. These T1-SP10 peptides can stimulate both cell-mediated and humoral i ... Full text Link to item Cite

Characterization of a CD6 ligand(s) expressed on human- and murine-derived cell lines and murine lymphoid tissues.

Journal Article Cell Immunol · October 15, 1994 CD6, a type I cell surface glycoprotein expressed predominantly by thymocytes and mature T lymphocytes, becomes phosphorylated on tyrosine residues following T cell activation and has been implicated as an accessory molecule in T cell activation. The purpo ... Full text Link to item Cite

The c-kit proto-oncogene receptor is expressed on a subset of human CD3-CD4-CD8- (triple-negative) thymocytes.

Journal Article Exp Hematol · September 1994 The c-kit receptor is a tyrosine-kinase transmembrane receptor first identified as an oncogene in the HZ4-feline leukemia virus and later found to be important in hematopoiesis in mice. The ligand for this receptor (Steel factor) can stimulate hematopoiesi ... Link to item Cite

From the Institute of Medicine.

Journal Article JAMA · August 10, 1994 Full text Link to item Cite

NMR-derived solution conformations of a hybrid synthetic peptide containing multiple epitopes of envelope protein gp120 from the RF strain of human immunodeficiency virus.

Journal Article Biochemistry · March 1, 1994 Solution conformations of a 40-residue hybrid peptide containing T-helper epitopes and B-cell determinants from envelope glycoprotein gp120 of human immunodeficiency virus (HIV) have been investigated with NMR. Peptides of this general design are highly im ... Full text Link to item Cite

Human early T-cell differentiation: Discussion

Journal Article Research in Immunology · January 1, 1994 Cite

Engraftment of human synovium into severe combined immune deficient mice. Migration of human peripheral blood T cells to engrafted human synovium and to mouse lymph nodes.

Journal Article J Immunol · December 15, 1993 To determine the feasibility of using the C.B-17 scid/scid (severe combined immune deficient, SCID) mouse as a recipient of human synovial xenografts, we have engrafted human synovium under the renal capsule of SCID mice, and determined synovial graft surv ... Link to item Cite

Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies.

Journal Article J Immunol · December 1, 1993 CD44 molecules are comprised of multiple alternatively spliced forms and are associated with diverse functions such as mediation of carcinoma metastasis and T cell coactivation. To study the function of individual CD44 isoforms, we have transfected CD44 is ... Link to item Cite

Synthetic peptide in mineral oil adjuvant elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes in rhesus monkeys.

Journal Article J Immunol · November 1, 1993 In view of the importance of cell-associated virus in AIDS virus transmission, an HIV vaccine should be able to induce a virus-specific CTL response. Traditional subunit vaccines have not elicited virus-specific CD8+ MHC class I-restricted CTL. We have use ... Link to item Cite

Cell adhesion molecules involved in intrathymic T cell development.

Journal Article Semin Immunol · August 1993 During stem cell migration to the thymus, intrathymic maturation of T cells, and emigration of mature T cells out of the thymus, intercellular interactions of developing T cells with a myriad of cell types are required for normal T cell development. Interc ... Full text Link to item Cite

Induction of HIVMN neutralizing antibodies in primates using a prime-boost regimen of hybrid synthetic gp120 envelope peptides.

Journal Article J Immunol · August 1, 1993 We have tested synthetic peptides composed of Th (T1) and V3 loop B cell neutralizing determinants [SP10 MN(A)] of HIVMN gp120 and the fusogenic (F) domain of gp41 as immunogens in rhesus monkeys. After two immunizations with either HIV env peptide T1-SP10 ... Link to item Cite

Scientific and social issues of human immunodeficiency virus vaccine development.

Journal Article Science · May 28, 1993 Development of a preventive immunogen for human immunodeficiency virus (HIV) infection is a national priority. The complexities associated with HIV host-virus interactions, coupled with the rapid progression of the HIV epidemic worldwide, have necessitated ... Full text Link to item Cite

The future of rheumatoid arthritis treatment.

Journal Article Bull Rheum Dis · April 1993 Research into the molecular mechanisms of immunological diseases and the development of more specific therapies are moving ahead simultaneously at a rapid pace. This information may provide a better paradigm for understanding the pathogenesis and the prosp ... Link to item Cite

Analysis of corneal and conjunctival microenvironments using monoclonal antibodies.

Journal Article Invest Ophthalmol Vis Sci · April 1993 PURPOSE: The authors phenotypically compared epithelial and nonepithelial components of human corneal and conjunctival microenvironments using a panel of monoclonal antibody reagents that included markers of epithelial cell maturation, markers of mesoderma ... Link to item Cite

Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein.

Journal Article J Exp Med · March 1, 1993 The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many virus and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we h ... Full text Link to item Cite

T cell CD7 mRNA expression is regulated by both transcriptional and post-transcriptional mechanisms.

Journal Article Int Immunol · February 1993 The CD7 molecule is a 40 kDa member of the Ig superfamily that is acquired early in human T cell ontogeny. Because of the putative three-dimensional structure of CD7 and its presence on T cell precursors, it has been postulated that CD7 serves as an adhesi ... Full text Link to item Cite

Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation.

Journal Article J Immunol · December 15, 1992 Treatment of T cells with the cysteine protease bromelain has been widely used to enhance the binding of human T cells to human E (autologous E rosettes) and has been shown to remove surface T cell CD44 molecules. Ligand binding to CD44 has been shown to m ... Link to item Cite

Mapping of homologous, amino-terminal neutralizing regions of human T-cell lymphotropic virus type I and II gp46 envelope glycoproteins.

Journal Article J Virol · October 1992 Twelve synthetic peptides containing hydrophilic amino acid sequences of human T-cell lymphotropic virus type I (HTLV-I) envelope glycoprotein were coupled to tetanus toxoid and used to raise epitope-specific antisera in goats and rabbits. Low neutralizing ... Full text Link to item Cite

In vivo models of human lymphopoiesis and autoimmunity in severe combined immune deficient mice.

Journal Article J Clin Immunol · September 1992 The discovery of the SCID mouse mutation has been an important advance for the study of human lymphopoiesis and autoimmunity. Further work in the SCID mouse models described in this review should yield important new information related to transplantation o ... Full text Link to item Cite

COGAN SYNDROME - CLINICAL-FEATURES AND OUTCOMES

Journal Article ARTHRITIS AND RHEUMATISM · September 1, 1992 Link to item Cite

Increase in TCR gamma delta T lymphocytes in synovia from rheumatoid arthritis patients with active synovitis.

Journal Article J Clin Immunol · March 1992 To determine the relative presence of TCR gamma delta+ and TCR alpha beta+ T cells in synovial tissue from patients with various types of inflammatory synovitis and in tissues from patients with a number of chronic T cell-mediated conditions, we stained fr ... Full text Link to item Cite

Regulation of cytokine production in the human thymus: epidermal growth factor and transforming growth factor alpha regulate mRNA levels of interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6 in human thymic epithelial cells at a post-transcriptional level.

Journal Article J Exp Med · November 1, 1991 Human thymic epithelial (TE) cells produce interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6, cytokines that are important for thymocyte proliferation. The mRNAs for these cytokines are short-lived and are inducible by multiple stimuli. Thus, the stead ... Full text Link to item Cite

Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides.

Journal Article Proc Natl Acad Sci U S A · November 1, 1991 The generation of antiviral cytotoxic T lymphocytes (CTLs) is a critical component of the immune response to viral infections. A safe and nontoxic vaccine for AIDS would optimally use a carrier-free synthetic peptide immunogen containing only components of ... Full text Link to item Cite

Measurement of an adhesion molecule as an indicator of inflammatory disease activity. Up-regulation of the receptor for hyaluronate (CD44) in rheumatoid arthritis.

Journal Article Arthritis Rheum · November 1991 The hyaluronate receptor (CD44) molecule is a multifunctional cell surface protein involved in T cell activation, monocyte cytokine release, fibroblast locomotion, and lymphocyte binding to high endothelial venules. To study the roles CD44 molecules play i ... Full text Link to item Cite

Induction of T cell CD7 gene transcription by nonmitogenic ionomycin-induced transmembrane calcium flux.

Journal Article J Immunol · October 15, 1991 The CD7 molecule is a 40-kDa member of the Ig superfamily that has structural homology to the murine Thy-1 molecule and is acquired early in human T cell ontogeny. Previous studies have demonstrated that expression of the CD7 molecule is markedly up-regula ... Link to item Cite

Thymic microenvironment induces HIV expression. Physiologic secretion of IL-6 by thymic epithelial cells up-regulates virus expression in chronically infected cells.

Journal Article J Immunol · October 15, 1991 The hallmark of infection with HIV-1 is progressive depletion and qualitative dysfunction of the CD4+ Th cell population in infected individuals. Clinical trials of antiretroviral agents have shown that, despite suppression of virus replication, regenerati ... Link to item Cite

Analysis of clones derived from human CD7+CD4-CD8-CD3- thymocytes.

Journal Article Int Immunol · October 1991 The differentiation of human thymocyte precursors was studied by analysis of clonal progeny of CD4-CD8-CD3- (triple negative or TN) thymocytes. Using a culture system of phytohemagglutinin, IL-2, and irradiated allogeneic lymphoid feeder cells, we found th ... Full text Link to item Cite

A tyrosine kinase physically associates with the beta-subunit of the human IL-2 receptor.

Journal Article J Immunol · August 15, 1991 Cell surface expression of the high affinity IL-2R regulates, in part, the proliferative response occurring in Ag- or mitogen-activated T cells. The functional high affinity IL-2R is composed of at least two distinct ligand-binding components, IL-2R alpha ... Link to item Cite

The specialized centers of research in rheumatoid arthritis. Recent progress and prospects for future advances.

Journal Article Hum Immunol · June 1991 Specialized Centers of Research (SCOR) in arthritis are interdisciplinary research programs to investigate disease pathogenesis as well as advance diagnosis and treatment. A recent meeting of investigators from the three SCOR programs in rheumatoid arthrit ... Full text Link to item Cite

The Duke University Arthritis Center.

Journal Article N C Med J · May 1991 The Duke University Arthritis Center has brought together both clinicians and basic scientists into a common structure to achieve a singular goal--that of improving the health and welfare of patients with immune-mediated diseases in North Carolina and surr ... Link to item Cite

ANALYSIS OF CLONAL PROGENY OF HUMAN T-CELL PRECURSORS

Journal Article FASEB JOURNAL · March 19, 1991 Link to item Cite

Isolation and characterization of the genomic human CD7 gene: structural similarity with the murine Thy-1 gene.

Journal Article Proc Natl Acad Sci U S A · January 15, 1991 The human CD7 molecule is a 40-kDa member of the immunoglobulin gene superfamily that is expressed on T-lymphoid and myeloid precursors in fetal liver and bone marrow. CD7 is also expressed on T lymphocytes in multiple stages of T-cell development, includi ... Full text Link to item Cite

Successful engraftment of human postnatal thymus in severe combined immune deficient (SCID) mice: differential engraftment of thymic components with irradiation versus anti-asialo GM-1 immunosuppressive regimens.

Journal Article J Exp Med · January 1, 1991 To develop a model of human thymus growth in vivo, we have implanted postnatal human thymus under the renal capsule of severe combined immune deficient (SCID) mice and assayed for graft survival and graft characteristics 1-3 mo after engraftment. Three gro ... Full text Link to item Cite

Analysis of clones derived from human CD7+CD4-CD8-CD3- thymocytes

Journal Article International Immunology · 1991 The differentiation of human thymocyte precursors was studied by analysis of clonal progeny of CD4-CD8-CD3- (triple negative or TN) thymocytes. Using a culture system of phytohemagglutinin, IL-2, and irradiated allogeneic lymphoid feeder cells, we found th ... Cite

SIV vaccine protection of rhesus monkeys.

Journal Article Biotechnol Ther · 1991 Rhesus macaques (M. mulatta), immunized with an inactivated whole SIVmac vaccine and muramyl dipeptide or Freund's incomplete adjuvant, were protected against IV challenge infection with 10 animal infectious doses of the homologous virus. The protection in ... Link to item Cite

Constitutive expression of a groEL-related protein on the surface of human gamma/delta cells.

Journal Article J Exp Med · December 1, 1990 Rabbit antibodies to hsp58 (P1), the human homologue of the Escherichia coli stress protein groEL, react specifically in indirect immunofluorescence and complement-dependent microcytoxicity experiments with a cell surface antigen expressed constitutively b ... Full text Link to item Cite

Human thymic epithelial cells produce IL-6, granulocyte-monocyte-CSF, and leukemia inhibitory factor.

Journal Article J Immunol · November 15, 1990 The development of conditions for culturing normal human thymic epithelial (TE) cells free from contaminating stromal cells has allowed us to characterize a number of cytokines produced by TE cells. Using cDNA probes for human IL-6, granulocyte-monocyte-CS ... Link to item Cite

EVALUATION OF V3 REGION BASED SYNTHETIC PEPTIDE INOCULA AS VACCINES FOR HIV-1 AND SIV

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

Synthetic peptides containing T and B cell epitopes from human immunodeficiency virus envelope gp120 induce anti-HIV proliferative responses and high titers of neutralizing antibodies in rhesus monkeys.

Journal Article J Immunol · October 15, 1990 We have previously described a synthetic peptide (T1-SP10) derived from two noncontiguous regions of HTLVIIIB envelope gp120 (T1, amino acids 428-443; SP10, amino acids 303-321) that induced type-specific anti-HIV neutralizing antibodies and T cell prolife ... Link to item Cite

Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion.

Journal Article Proc Natl Acad Sci U S A · October 1990 Individuals infected by the human immunodeficiency virus type 1 (HIV-1) demonstrate progressive depletion and qualitative dysfunction of the helper T4 (CD4+) cell population. Mechanisms proposed for attrition of CD4+ T cells include direct cytopathicity of ... Full text Link to item Cite

Expression of early activation antigen (CD69) during human thymic development.

Journal Article Clin Exp Immunol · September 1990 The novel early activation antigen, EA1, has been shown to be induced by mitogens, antigens and the tumour promoter, phorbol myristate acetate (PMA), on human lymphocytes. This antigen has been designated to be CD69. EA1 has also been shown to be expressed ... Full text Link to item Cite

Ligand binding to the LFA-3 cell adhesion molecule induces IL-1 production by human thymic epithelial cells.

Journal Article J Immunol · June 15, 1990 We have shown that human thymic epithelial (TE) cells produce IL-1 alpha, IL-1 beta, and TE cells bind to thymocytes by CD2 and LFA-1 molecules on thymocytes and LFA-3, ICAM-1 on TE cells. We investigated whether ligand binding to LFA-3 on human TE cells c ... Link to item Cite

The role of adhesion molecules in epithelial-T-cell interactions in thymus and skin.

Journal Article J Invest Dermatol · June 1990 Interaction of T lymphocytes with other cell types is important for normal T-cell development and function. Recently, a number of adhesion molecules important in T-cell interactions with other cell types have been defined. In this paper we review the role ... Full text Link to item Cite

Elimination of malignant clonogenic T cells from human bone marrow using chemoimmunoseparation with 2'-deoxycoformycin, deoxyadenosine and an immunotoxin.

Journal Article Bone Marrow Transplant · June 1990 Autologous bone marrow transplantation may contribute to the treatment of several types of lymphoreticular malignancies. Recent studies have suggested that a combination of chemoseparation and immunoseparation may be more effective than either modality alo ... Link to item Cite

Thymocyte LFA-1 and thymic epithelial cell ICAM-1 molecules mediate binding of activated human thymocytes to thymic epithelial cells.

Journal Article J Immunol · April 15, 1990 We have investigated the binding in vitro of activated thymocytes to thymic epithelial (TE) cells, and studied the effect of up-regulation of TE cell surface intracellular adhesion molecule 1 (ICAM-1) and HLA-DR by IFN-gamma on the ability of TE cells to b ... Link to item Cite

Localization of collagenase mRNA in rheumatoid arthritis synovium by in situ hybridization histochemistry.

Journal Article J Clin Immunol · January 1990 Collagenase has been implicated as playing an important role in the connective tissue destruction that is a major feature of rheumatoid arthritis. Numerous cell types in the hyperplastic rheumatoid synovium are capable of synthesizing collagenase. Past stu ... Full text Link to item Cite

Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation.

Journal Article J Immunol · January 1, 1990 The CD44 inhibitor Lutheran [In(Lu)]-related p80 molecule has recently been shown to be identical to the Hermes-1 lymphocyte homing receptor and to the human Pgp-1 molecule. We have determined the effect of addition of CD44 antibodies to in vitro activatio ... Link to item Cite

Human thymic epithelium and T cell development: current issues and future directions.

Journal Article Thymus · 1990 The human thymus develops early in fetal gestation with morphologic maturity reached by the beginning of the second trimester. TE3+ cortical thymic epithelium is most likely derived from endodermal third pharyngeal pouch, while A2B5/TE4+ medullary and subc ... Link to item Cite

Human intrathymic T cell differentiation.

Journal Article Semin Immunol · January 1990 The human thymus develops early on in fetal gestation with morphologic maturity reached by the beginning of the second trimester. Endodermal epithelial tissue from the third pharyngeal pouch gives rise to TE3+ cortical thymic epithelium while ectodermal ep ... Link to item Cite

CD44 antibody against In(Lu)-related p80, lymphocyte-homing receptor molecule inhibits the binding of human erythrocytes to T cells.

Journal Article J Immunol · December 15, 1989 The cluster of differentiation 44 (CD44) Ag system, originally described in brain and mature T cells, has been subsequently shown to be identical with the human lymphocyte homing-receptor defined by the Hermes-1 antibody and to be involved in T cell/endoth ... Link to item Cite

The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif.

Journal Article Proc Natl Acad Sci U S A · December 1989 We have identified the human gene, SCL. We discovered this gene because of its involvement in a chromosomal translocation associated with the occurrence of a stem cell leukemia manifesting myeloid and lymphoid differentiation capabilities. Here we report t ... Full text Link to item Cite

Characterization of the surface topography and putative tertiary structure of the human CD7 molecule.

Journal Article J Immunol · December 1, 1989 The CD7 gp40 molecule is a member of the Ig gene superfamily and is expressed on T cell precursors before their entry into the thymus during fetal development. N-terminal amino acids 1-107 of CD7 are highly homologous to Ig kappa-L chains whereas the carbo ... Link to item Cite

CD44--a molecule involved in leukocyte adherence and T-cell activation.

Journal Article Immunol Today · December 1989 The study of cell surface molecules that are involved in interactions between immune and non-hematopoietic cells in various microenvironments is currently an area of great interest. One molecule that appears to be involved in multiple steps of normal immun ... Full text Link to item Cite

Immature human thymocytes can be driven to differentiate into nonlymphoid lineages by cytokines from thymic epithelial cells.

Journal Article Proc Natl Acad Sci U S A · October 1989 The signals and cellular interactions required for hematopoietic stem-cell commitment to the T lineage are unknown, yet are central to understanding the early stages of normal T-cell development. To study the differentiative capacity of T-cell precursors, ... Full text Link to item Cite

Immunodominant sites of human T cell lymphotropic virus type 1 envelope protein for murine helper T cells.

Journal Article J Immunol · September 15, 1989 HTLV-I (human T cell lymphotropic virus type 1) is the retrovirus causally related to adult T cell leukemia/lymphoma and is also associated with a neurological disorder, tropical spastic paraparesis, or HTLV-I-associated myelopathy. The development of thes ... Link to item Cite

Polyvalent human immunodeficiency virus synthetic immunogen comprised of envelope gp120 T helper cell sites and B cell neutralization epitopes.

Journal Article J Immunol · May 15, 1989 In previous studies, we have used antisera raised to envelope (env)-gene-encoded synthetic peptides to identify a region of (HIV) glycoprotein (gp) 120 env protein designated SP10 that contains a type-specific neutralizing determinant. To develop a polyval ... Link to item Cite

Human postnatal CD4- CD8- CD3- thymic T cell precursors differentiate in vitro into T cell receptor delta-bearing cells.

Journal Article J Immunol · May 1, 1989 The signals required for activation and the differentiation of human triple negative postnatal thymocytes were studied in vitro. Highly purified populations of CD4-, CD8-, CD3- (triple negative) thymocytes were isolated by combined panning and preparative ... Link to item Cite

Monoclonal antibodies against the CD44 [In(Lu)-related p80], and Pgp-1 antigens in man recognize the Hermes class of lymphocyte homing receptors.

Journal Article J Immunol · March 15, 1989 An 85- to 95 kDa class of lymphocyte surface molecules, defined in man by antibodies of the Hermes series, is involved in lymphocyte binding to high endothelial venules and is likely of central importance in the process of lymphocyte homing. In this report ... Link to item Cite

Ontogeny of T-cell precursors: a model for the initial stages of human T-cell development.

Journal Article Immunol Today · March 1989 Although most investigators agree that the CD4- CD8- CD3- thymocyte subset represents the most immature intrathymic T cell capable of repopulating the thymus in vivo, little is known of the earliest stages of human T-cell development. Using mAbs to hematop ... Full text Link to item Cite

Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript.

Journal Article Proc Natl Acad Sci U S A · March 1989 We have studied a leukemic stem-cell line, DU.528, that is able to differentiate into myeloid and lymphoid cells. The leukemic cells have a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), which we have molecularly cloned and sequenced. Initia ... Full text Link to item Cite

Removal of fibroblasts from human epithelial cell cultures with use of a complement fixing monoclonal antibody reactive with human fibroblasts and monocytes/macrophages.

Journal Article J Invest Dermatol · February 1989 A complement fixing IgM monoclonal antibody (1B10) that reacts with surface membrane molecules of human fibroblasts, tissue macrophages, and peripheral monocytes was produced. In Western blot analysis of detergent extracts of cultured human foreskin fibrob ... Full text Link to item Cite

Mapping of immunogenic regions of human T cell leukemia virus type I (HTLV-I) gp46 and gp21 envelope glycoproteins with env-encoded synthetic peptides and a monoclonal antibody to gp46.

Journal Article J Immunol · February 1, 1989 Antigenic sites on human T cell leukemia virus type I (HTLV-I) gp46 and gp21 envelope glycoproteins that are immunogenic in man were studied with envelope gene (env)-encoded synthetic peptides and a mAb to HTLV-I gp46 envelope glycoprotein. Antibodies in 7 ... Link to item Cite

CD7+, CD4-, CD8- acute leukemia: a syndrome of malignant pluripotent lymphohematopoietic cells.

Journal Article Blood · February 1989 Following our initial observation of in vivo conversion of CD7+, CD4-, CD8- acute lymphoblastic leukemia (ALL) cells from lymphoid to myeloid lineages (Proc Natl Acad Sci (USA) 81:253, 1984) we have studied eight additional cases of ALL with this leukemic ... Link to item Cite

Immunohistologic analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment.

Journal Article Arthritis Rheum · January 1989 Antigen-independent binding of T lymphocytes to a variety of cell types has been shown to be mediated by receptor-ligand pairs of adhesion molecules. In forms of inflammatory synovitis (including rheumatoid arthritis), T cells home to synovium, become acti ... Full text Link to item Cite

Human postnatal CD4- CD8- CD3- thymic T cell precursors differentiate in vitro into T cell receptor δ-bearing cells

Journal Article Journal of Immunology · 1989 The signals required for activation and the differentiation of human triple negative postnatal thymocytes were studied in vitro. Highly purified populations of CD4-, CD8-, CD3- (triple negative) thymocytes were isolated by combined panning and preparative ... Cite

Analysis of expression of CD2, CD3, and T cell antigen receptor molecules during early human fetal thymic development.

Journal Article J Immunol · December 1, 1988 To define early stages of T cell maturation during human fetal thymic development, we have used mAb reactive with CD2, CD3, and TCR molecules in indirect immunofluorescence assays on a series of early human fetal thymic specimens. Using a technique of quan ... Link to item Cite

Purified lymphocyte function-associated antigen-3 (LFA-3) activates human thymocytes via the CD2 pathway.

Journal Article J Immunol · November 1, 1988 Defining the cellular and molecular mechanisms of interaction of developing thymocytes with nonlymphoid cells of the thymic microenvironment is critical for understanding normal thymus function. We have previously shown that the CD2/LFA-3 adhesion pathway ... Link to item Cite

A novel activation pathway for mature thymocytes. Costimulation of CD2 (T,p50) and CD28 (T,p44) induces autocrine interleukin 2/interleukin 2 receptor-mediated cell proliferation.

Journal Article J Exp Med · October 1, 1988 Prior studies have shown that thymocytes, unlike peripheral T cells, do not proliferate in response to mitogenic combinations of anti-CD2 mAbs. The present study demonstrated that stimulation by a mitogenic anti-CD2 combination (9-1 plus 9.6) with anti-CD2 ... Full text Link to item Cite

Demonstration of phenotypic abnormalities of thymic epithelium in thymoma including two cases with abundant Langerhans cells.

Journal Article Am J Pathol · September 1988 A panel of monoclonal antibodies that phenotypically define stages of normal human thymic epithelial (TE) cell maturation was used to compare thymic epithelium of nine thymomas with hyperplastic thymic epithelium in myasthenia gravis (MG) and thymic epithe ... Link to item Cite

Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues.

Journal Article J Exp Med · September 1, 1988 During early fetal development, T cell precursors home from fetal yolk sac and liver to the epithelial thymic rudiment. From cells that initially colonize the thymus arise mature T cells that populate T cell zones of the peripheral lymphoid system. Whereas ... Full text Link to item Cite

Human thymic epithelial cells produce granulocyte and macrophage colony-stimulating factors.

Journal Article J Immunol · August 15, 1988 The development of culture conditions for growing normal human thymic epithelial (TE) cells free from contamination with other stromal cells has allowed us to identify and characterize TE cell-derived cytokines. In this study, we report that cultured human ... Link to item Cite

Synovial microenvironment-T cell interactions. Human T cells bind to fibroblast-like synovial cells in vitro.

Journal Article Arthritis Rheum · August 1988 Synovitis in rheumatoid arthritis is characterized by infiltration of the synovium by T and B lymphocytes and monocytes, as well as by the proliferation of synovial lining cells, fibroblasts, and endothelial cells. To study synovial cell-T cell interaction ... Full text Link to item Cite

Human T-cell lymphotropic virus I and adult T-cell leukemia: report of a cluster in North Carolina.

Journal Article Am J Med · July 1988 PURPOSE: Human adult T-cell leukemia-lymphoma is a malignant, proliferative disease of CD4+ lymphocytes associated with infection with human T-cell lymphotropic virus type I (HTLV-I). Following the presentation of a patient who was infected with the virus, ... Full text Link to item Cite

Human thymic epithelial cells directly induce activation of autologous immature thymocytes.

Journal Article Proc Natl Acad Sci U S A · May 1988 To study the role that epithelial cells of the thymic microenvironment play in promoting activation of immature CD7+, CD2+, CD4-, CD8- (double-negative) human thymocytes, we have isolated thymocyte subsets from normal postnatal thymus and have cocultured a ... Full text Link to item Cite

CD2 PATHWAY ACTIVATION OF HUMAN CD4-THYMOCYTES, CD8-THYMOCYTES

Journal Article CLINICAL RESEARCH · April 1, 1988 Link to item Cite

HUMAN THYMIC EPITHELIAL-CELLS PRODUCE GRANULOCYTE AND MACROPHAGE COLONY-STIMULATING FACTORS

Journal Article JOURNAL OF INVESTIGATIVE DERMATOLOGY · April 1, 1988 Link to item Cite

A NOVEL ACTIVATION PATHWAY FOR MATURE THYMOCYTES

Journal Article FASEB JOURNAL · March 20, 1988 Link to item Cite

Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides.

Journal Article Proc Natl Acad Sci U S A · March 1988 A synthetic peptide (SP-10-IIIB) with an amino acid sequence [Cys-Thr-Arg-Pro-Asn-Asn-Asn-Thr-Arg-Lys-Ser-Ile-Arg-Ile-Gln-Arg-Gly-Pro -Pro-Gly-(Tyr); amino acids 303-321] from the human immunodeficiency virus (HIV) isolate human T-cell lymphotropic virus t ... Full text Link to item Cite

Differentiation of human T cells.

Journal Article Clin Lab Med · March 1988 This article discusses the ontogeny of human T cells along with the relationship of normal T-cell maturation to the development of various malignant T-cell syndromes. The impact of monoclonal antibody technology, the discovery of the T-cell receptor for an ... Link to item Cite

Monoclonal antibodies to CD2 and lymphocyte function-associated antigen 3 inhibit human thymic epithelial cell-dependent mature thymocyte activation.

Journal Article J Immunol · October 15, 1987 Recent study of human thymocyte-thymic epithelial (TE) cell interactions has demonstrated that thymocytes bind to TE cells, and a consequence of this binding is the provision of accessory cell signals by TE cells for phytohemagglutinin (PHA)-induced mature ... Link to item Cite

Epithelial-thymocyte interactions in human thymus.

Journal Article Hum Immunol · October 1987 Our data demonstrate that the epithelial component of the human thymic microenvironment is not an inert cell type, but rather is capable of being directly involved in the promotion of both early and late stages of T-cell maturation. Data from our laborator ... Full text Link to item Cite

Combined chemoseparation and immunoseparation of clonogenic T lymphoma cells from human bone marrow using 2'-deoxycoformycin, deoxyadenosine, 3A1 monoclonal antibody, and complement.

Journal Article Cancer Res · September 1, 1987 Chemoseparation and immunoseparation techniques have been combined to eliminate malignant clonogenic T lymphoma cells from human bone marrow. Incubation with 5 microM 2'-deoxycoformycin and 500 microM deoxyadenosine has eliminated 2 logs of HSB-2 T lymphom ... Link to item Cite

Polyspecific reactivity of a murine monoclonal antibody that binds to nuclear matrix-associated, chromatin-bound autoantigens.

Journal Article Clin Immunol Immunopathol · August 1987 To investigate polyspecific autoantibody interactions, we have characterized the binding of a cloned murine monoclonal IgM antibody termed (RTE-23) of strain BALB/c origin. By indirect immunofluorescence this antibody displayed a nuclear speckled and perip ... Full text Link to item Cite

Monoclonal antibodies to a human islet cell surface glycoprotein: 4F2 and LC7-2.

Journal Article Endocrinology · June 1987 Monoclonal antibodies 4F2 and LC7-2 react with a cell surface differentiation antigen expressed by the endocrine cells of the human pancreatic islet, but not by the acinar pancreatic, ductular, vascular, or stromal connective tissue cells. Western immunobl ... Full text Link to item Cite

Human thymic epithelial cells produce interleukin 1.

Journal Article J Immunol · April 15, 1987 Although the thymus plays a critical role in generation of immunocompetent T lymphocytes, the precise role of the epithelial component of the thymus in the induction of T cell proliferation and maturation remains unknown. Since interleukin 1 (IL 1) is requ ... Link to item Cite

A conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope.

Journal Article Proc Natl Acad Sci U S A · April 1987 A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids f ... Full text Link to item Cite

Human thymic epithelial cells function as accessory cells for autologous mature thymocyte activation.

Journal Article J Immunol · February 1, 1987 Using human thymocytes and autologous thymic epithelial (TE) cells grown in vitro in long-term culture, we have found TE cells can function as accessory cells for mitogen-induced mature thymocyte activation. Tritiated thymidine incorporation, blast formati ... Link to item Cite

Thymocyte binding to human thymic epithelial cells is inhibited by monoclonal antibodies to CD-2 and LFA-3 antigens.

Journal Article J Immunol · January 15, 1987 With the use of cultured human thymic epithelial (TE) cells, we have previously shown that thymocytes bind to TE cells in suspension in a rosette-forming assay. To identify cell surface molecules involved in human TE-thymocyte rosette formation, we assayed ... Link to item Cite

Human erythrocyte antigens. III. Characterization of a panel of murine monoclonal antibodies that react with human erythrocyte and erythroid precursor membranes.

Journal Article Vox Sang · 1987 Human erythrocyte membrane proteins express antigens which serve as markers for erythroid differentiation as well as targets for human blood group alloantibodies. We have produced and characterized a new panel of five monoclonal antibodies to erythrocyte m ... Full text Link to item Cite

The thymic microenvironment. Characterization of in vitro differentiation of the IT26R21 rat thymic epithelial cell line.

Journal Article Differentiation · 1987 We have previously postulated an in vivo pathway of thymic epithelial (TE) cell maturation in pre- and postnatal thymus, whereby endocrine medullary TE cells terminally differentiate to form Hassall's bodies. Epithelial-cell differentiation has been well d ... Full text Link to item Cite

BIOLOGY OF THE NORMAL AND LEUKEMIC CD-7+ STEM-CELL

Journal Article JOURNAL OF CELLULAR BIOCHEMISTRY · January 1, 1987 Link to item Cite

Human medullary thymocyte p80 antigen and In(Lu)-related p80 antigen reside on the same protein.

Journal Article Hum Immunol · November 1986 Study of human T lymphocyte differentiation antigens with monoclonal antibodies has led to the identification of two antigens shared by erythrocytes and leukocytes. The protein (p80) defined by A1G3 antibody has previously been shown to be acquired during ... Full text Link to item Cite

Immunoglobulin and T-cell receptor gene rearrangement and expression in human lymphoid leukemia cells at different stages of maturation.

Journal Article Proc Natl Acad Sci U S A · November 1986 The use of probes to genes (IG and TCRB) encoding immunoglobulins (IG) and the beta chain of the T-cell antigen receptor (TCRB), respectively, have become a sensitive means to assess clonality and lineage in lymphoid malignancies. It has become apparent th ... Full text Link to item Cite

Characterization of a monoclonal antibody, RTE-21, that binds to keratohyalin granule-associated proteins in epithelial cells of human skin and thymus.

Journal Article Clin Immunol Immunopathol · October 1986 The role of skin and thymic epithelium in the promotion of T-cell activation and maturation is currently an area of great interest. In thymus, epithelium is located in the cortex, medulla, and in medullary epithelial swirls called Hassall's bodies. During ... Full text Link to item Cite

Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro.

Journal Article Proc Natl Acad Sci U S A · September 1986 The thymus plays a critical role in the generation of immunocompetent T lymphocytes. In the thymus, lymphocytes are in close contact with epithelial cells, and this contact is necessary for T-cell maturation. Using cultured human thymic epithelial (TE) cel ... Full text Link to item Cite

C-terminal region of human T cell lymphotropic virus type I (HTLVI) p19 core protein is immunogenic in humans and contains an HTLVI-specific epitope.

Journal Article J Immunol · April 1, 1986 To study the human host response to viral structural proteins during HTLV type I infection, five synthetic peptides matching the N-terminal and C-terminal regions of HTLVI p19 core protein were used to identify antigenic sites on p19 that were immunogenic ... Link to item Cite

DEMONSTRATION OF THYMIC EPITHELIAL-CELL DIFFERENTIATION INVITRO

Journal Article CLINICAL RESEARCH · April 1, 1986 Link to item Cite

HUMAN THYMIC EPITHELIAL-CELLS PRODUCE INTERLEUKIN-1 (IL-1)

Journal Article FEDERATION PROCEEDINGS · March 5, 1986 Link to item Cite

Diagnostic and therapeutic approach to the patient with vasculitis.

Journal Article Med Clin North Am · March 1986 This article presents an approach to the diagnosis and therapy of patients with vasculitis. Effective treatment of patients with vasculitis requires a systemic approach to diagnosis and classification of disease, evaluation of the extent of organ system in ... Full text Link to item Cite

The human thymic microenvironment: thymic epithelium contains specific keratins associated with early and late stages of epidermal keratinocyte maturation.

Journal Article Differentiation · 1986 Normal T-cell development is dependent on interactions with the thymic microenvironment; thymic epithelial cells are thought to play a key role in the induction of thymocyte maturation, both through direct contact and, indirectly, via thymic hormone secret ... Full text Link to item Cite

Antibody against T lymphoblastic leukemia-associated antigen (3-40) identifies vimentin and keratin intermediate filaments in normal cells.

Journal Article Blood · September 1985 Antibody 3-40 defines a 35- to 40-kd surface antigen present on T lymphoblastic leukemia (T-ALL) cells that is absent on normal hematopoietic cells (Naito et al, Blood 62:852, 1983). Using immunoblot analysis of cytoskeletal proteins and indirect immunoflu ... Link to item Cite

Human T cell antigen expression during the early stages of fetal thymic maturation.

Journal Article J Immunol · September 1985 Human thymus tissue was examined from 7 wk of gestation through birth for the expression of antigens reacting with a panel of anti-T cell monoclonal antibodies. Additionally, the reactivities of reagents against the transferrin receptor, against leukocytes ... Link to item Cite

In vitro growth and phenotypic characterization of mesodermal-derived and epithelial components of normal and abnormal human thymus.

Journal Article Hum Immunol · July 1985 Long-term in vitro cultures of human thymic tissue were established and phenotypically characterized using monoclonal reagents that define distinct components of the human thymic microenvironment. The epithelial component of the thymus, defined by monoclon ... Full text Link to item Cite

Monoclonal antibodies reactive with human T cell lymphotropic virusI (HTLVI) p19 internal core protein: cross-reactivity with normal tissues and differential reactivity with HTLV types I and II.

Journal Article J Immunol · July 1985 Three monoclonal antibodies to human T cell lymphotropic virus type I (HTLVI) p19 internal core protein, designated as alpha HTLV-2, 3, and 4, have been developed. In indirect immunofluorescence (IF) assays, these antibodies reacted with acetone-fixed cyto ... Link to item Cite

Expression of antigens by cultured epithelial cells: comparison of epidermis and thymic epithelium.

Journal Article J Invest Dermatol · July 1985 We have established long term in vitro cultures of human thymic epithelium and human epidermis free of contaminating fibroblasts. The cultured cells were examined using a panel of monoclonal antibodies which were raised against human thymic stroma and reco ... Full text Link to item Cite

MONOCLONAL AUTOANTIBODIES TO KERATINS DISTINGUISH SUBSETS OF HUMAN-SKIN AND THYMIC EPITHELIUM

Journal Article JOURNAL OF INVESTIGATIVE DERMATOLOGY · January 1, 1985 Link to item Cite

Phenotypic and functional characterization of human malignant T cells.

Journal Article Semin Hematol · January 1985 Malignancies of thymus-derived (T) lymphocytes can be divided into two major groups: diseases of T cells expressing immature T cell markers (T-ALL, T cell lymphoblastic lymphoma) and diseases of malignant T cells expressing markers in a pattern similar to ... Link to item Cite

The human thymic microenvironment. Phenotypic characterization of Hassall's bodies with the use of monoclonal antibodies.

Journal Article J Immunol · January 1985 The human thymic microenvironment is important in promotion of T cell maturation, particularly during early stages of thymic ontogeny. Hassall's bodies (HB) are epithelial swirls in the human thymic medulla that are thought to be derived from endocrine med ... Link to item Cite

ONTOGENY OF HUMAN T-CELL ANTIGENS

Journal Article CLINICAL RESEARCH · January 1, 1985 Link to item Cite

SELECTIVE REMOVAL OF MALIGNANT B-CELL AND T-CELL NEOPLASMS FROM HUMAN-BONE MARROW

Journal Article INTERNATIONAL JOURNAL OF CELL CLONING · January 1, 1985 Link to item Cite

Selective inhibition of natural killer activity by the monoclonal antibodies OKT10 and VEP10 at the single cell level.

Journal Article Cell Immunol · October 15, 1984 The monoclonal antibodies, VEP10 and OKT10, which have been shown to recognize determinants on human natural killer (NK) cells, inhibit large granular lymphocyte (LGL) NK activity against K562, MOLT4, and CEM tumor target cells in the single cell conjugate ... Full text Link to item Cite

The human thymic microenvironment: cortical thymic epithelium is an antigenically distinct region of the thymic microenvironment.

Journal Article J Immunol · September 1984 The thymic microenvironment is a complex tissue essential for normal T cell maturation. Prothymocytes in the subcapsular cortical (SCC) region of the thymus undergo cell division and migrate to the inner cortex. The majority of cortical thymocytes cease di ... Link to item Cite

Human erythrocyte antigens: II. The In(Lu) gene regulates expression of an antigen on an 80-kilodalton protein of human erythrocytes.

Journal Article Blood · September 1984 We have previously shown that a murine monoclonal antibody (A3D8) identifies a human erythrocyte protein antigen whose expression is regulated by the Lutheran inhibitor [In(Lu)] gene. In the present study, we demonstrated by immunoprecipitation and Western ... Link to item Cite

Monoclonal antibody 4F2 reactive with basal layer keratinocytes: studies in the normal and a hyperproliferative state.

Journal Article J Invest Dermatol · September 1984 To establish a method for separating different keratinocyte subpopulations in the epidermis, we studied the specificity of monoclonal antibody 4F2 for keratinocytes. Preliminary screening experiments had previously demonstrated 4F2 reactivity with the epid ... Full text Link to item Cite

TEACHING EPIDEMIOLOGY IN MEDICAL SCHOOLS: A WORKABLE MODEL

Journal Article American Journal of Epidemiology · August 1984 Full text Cite

Ia+ T cells in new onset Graves' disease.

Journal Article J Clin Endocrinol Metab · August 1984 The Ia (immune-associated, DR) antigen is a cell surface glycoprotein which is absent on normal circulating T lymphocytes but present on activated T lymphocytes. We studied the expression of this antigen on circulating T lymphocytes from patients with untr ... Full text Link to item Cite

Early corneal findings in Cogan's syndrome.

Journal Article Ophthalmology · August 1984 We evaluated the ocular manifestations of Cogan's syndrome in 13 consecutive patients. The most frequent and earliest ocular finding was bilateral peripheral subepithelial keratitis consisting of faint, nummular lesions. The subepithelial keratitis was res ... Full text Link to item Cite

Rheumatoid arthritis and sterile corneal ulceration. Analysis of tissue immune effector cells and ocular epithelial antigens using monoclonal antibodies.

Journal Article Arthritis Rheum · June 1984 Tissue immune effector cells and epithelial surface antigens present in eye tissue of rheumatoid arthritis (RA) patients with sterile corneal ulceration were studied using a large panel of monoclonal antibodies. During periods of active corneal ulceration, ... Full text Link to item Cite

Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.

Journal Article Science · May 4, 1984 Peripheral blood lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that frequently precede AIDS (pre-AIDS) were grown in vitro with added T-cell growth factor and assayed for the expression and release o ... Full text Link to item Cite

Thymoma: lymphoid and epithelial components mirror the phenotype of normal thymus.

Journal Article Hum Pathol · April 1984 Six thymomas were studied with monoclonal and polyclonal antisera and an immunohistochemical technique to characterize the lymphocytic and epithelial components of the tumor. The T lymphocytes had characteristics of thymocytes, and cortico medullary differ ... Full text Link to item Cite

Monoclonal antibodies against human T cell leukemia-lymphoma virus (HTLV) p24 internal core protein. Use as diagnostic probes and cellular localization of HTLV.

Journal Article J Exp Med · April 1, 1984 Four monoclonal antibodies, human T cell leukemia-lymphoma virus (HTLV) 6, 7, 8, and 9, which react with the 24,000 dalton internal core protein of HTLVI, have been developed. These monoclonal antibodies reacted with only HTLV-infected cells and not with a ... Full text Link to item Cite

Phenotypic characterization and ontogeny of mesodermal-derived and endocrine epithelial components of the human thymic microenvironment.

Journal Article J Exp Med · April 1, 1984 Using murine monoclonal antibodies TE-4 and TE-7 raised against human thymic stroma, we identified two distinct and mutually exclusive thymic microenvironment components: the thymic endocrine epithelium (TE-4+) and mesodermal-derived fibrous stroma (TE-7+) ... Full text Link to item Cite

NK CELL LEUKEMIA - A HISTOLOGIC MIMIC OF MALIGNANT HISTIOCYTOSIS

Journal Article LABORATORY INVESTIGATION · January 1, 1984 Link to item Cite

Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2'-deoxycoformycin.

Journal Article Proc Natl Acad Sci U S A · January 1984 Selective failure of lymphoid development occurs in genetic deficiency of adenosine deaminase (ADA). We examined the in vivo effects of a potent inhibitor of ADA, 2'-deoxycoformycin, which was used to treat a patient with refractory acute leukemia. Unexpec ... Full text Link to item Cite

The human thymic microenvironment.

Journal Article Adv Immunol · 1984 Several major points should be emphasized that provide directions for future research. First, using monoclonal reagents we have been able to phenotypically identify four major regions of the human thymus microenvironment: the thymic capsule, interlobular s ... Full text Link to item Cite

Ia+ T cells in new onset Graves' disease

Journal Article Journal of Clinical Endocrinology and Metabolism · 1984 The Ia (immune-associated, DR) antigen is a cell surface glycoprotein which is absent on normal circulating T lymphocytes but present on activated T lymphocytes. We studied the expression of this antigen on circulating T lymphocytes from patients with untr ... Cite

Differentiation of human T lymphocytes. I. Acquisition of a novel human cell surface protein (p80) during normal intrathymic T cell maturation.

Journal Article J Immunol · September 1983 The thymus is thought to be the primary central lymphoid organ in which T cells mature. Although thymic cortical and medullary compartments are distinct histologically, few antigens have been described that are absolutely acquired during the presumed intra ... Link to item Cite

Cell lines producing human T-cell lymphoma virus show altered HLA expression.

Journal Article Nature · September 1, 1983 Human T-cell leukaemia/lymphoma virus (HTLV) can be identified in fresh and cultured T-lymphocytes from patients with adult T-cell malignancies. HLA typing of the peripheral blood lymphocytes and cultured cell lines from the patient from which the virus wa ... Full text Link to item Cite

Interaction of pokeweed mitogen with monocytes in the activation of human lymphocytes.

Journal Article Immunology · August 1983 The present study examines the role of monocytes in the in-vitro activation of human T cells and B cells by pokeweed mitogen (PWM). The T cell-dependent PWM-induced B-cell activation process was found to be monocyte dependent. Fluorescence-activated cell s ... Link to item Cite

Association of the human type C retrovirus with a subset of adult T-cell cancers.

Journal Article Cancer Res · August 1983 To determine whether the human T-cell lymphoma-leukemia virus (HTLV) is associated with particular cancers, patient sera were surveyed for HTLV-specific antibodies. An association was seen with aggressive cancers of mature T-cells, specifically Japanese ad ... Link to item Cite

Effect of thymectomy on peripheral lymphocyte subsets in myasthenia gravis: selective effect on T-cells in patients with thymic atrophy.

Journal Article J Immunol · August 1983 Myasthenia gravis (MG) is an autoimmune disease affecting nicotinic acetylcholine receptors. The clinical improvement that follows thymectomy in some myasthenic patients implicates thymic factors as well in the pathogenesis of MG. We have studied circulati ... Link to item Cite

Heterogeneity of acute lymphocytic leukemia cell surface markers as detected by monoclonal antibodies.

Journal Article J Natl Cancer Inst · July 1983 Monoclonal antibodies 3A1, 4F2, 5E9, OKT3, OKT6, and OKT8 were tested by flow microfluorometry for reactivity with cells from patients with T-cell or null cell acute lymphocytic leukemia (ALL). The 3A1 antibody reacted with a greater percentage of cells fr ... Link to item Cite

Human erythrocyte antigens. Regulation of expression of a novel erythrocyte surface antigen by the inhibitor Lutheran In(Lu) gene.

Journal Article J Clin Invest · June 1983 Our study describes a novel human erythrocyte protein antigen, the expression of which is regulated by the rare Lutheran inhibitor In(Lu) gene. We have produced a monoclonal antibody (A3D8) that bound strongly to erythrocytes from subjects with Lutheran ph ... Full text Link to item Cite

A monoclonal antibody reactive with a second epitope of the 67,000-dalton human T cell antigen.

Journal Article Hum Immunol · June 1983 Hybridomas were produced against the T-cell CLL derived-cell line, SKW3, by the fusion of hyperimmune spleen cells with P3 myeloma cells. One clone, designated DU-SKW3-1, was shown to produce a murine IgG2b antibody reactive with an antigen expressed on no ... Full text Link to item Cite

Chromosome mapping of human cell surface molecules: monoclonal anti-human lymphocyte antibodies 4F2, A3D8, and A1G3 define antigens controlled by different regions of chromosome 11.

Journal Article Somatic Cell Genet · May 1983 Monoclonal antibodies 4F2, A3D8, and A1G3, directed against cell surface antigens present on subsets of human cells, were used to identify the human chromosome regions that code for the antigenic determinants. Human fibroblasts expressed all three antigens ... Full text Link to item Cite

Relatedness by nucleic acid hybridization of new isolates of human T-cell leukemia-lymphoma virus (HTLV) and demonstration of provirus in uncultured leukemic blood cells.

Journal Article Virology · April 30, 1983 Human T-cell leukemia-lymphoma virus (HTLV) has now been isolated from many different patients with cutaneous T-cell lymphoma and leukemia, as judged by detection of media reverse transcriptase and virus particles and of antigenic determinants related to t ... Full text Link to item Cite

Identification of human T cell leukemia virus in a Japanese patient with adult T cell leukemia and cutaneous lymphomatous vasculitis.

Journal Article Proc Natl Acad Sci U S A · April 1983 We have identified a Japanese patient with adult T-cell leukemia (ATL) whose T cells in vitro produced the human T-cell leukemia virus (HTLV). This patient presented with lymphomatous arthritis and leukemia and subsequently developed skin lesions. Skin inv ... Full text Link to item Cite

Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny.

Journal Article J Exp Med · March 1, 1983 Using monoclonal antibody 12/1-2 against a 19,000-dalton human T cell leukemia virus (HTLV) protein (anti-p19), previously demonstrated to be reactive with HTLV-infected human cells, but not in numerous other uninfected cells, we found a reactive antigen t ... Full text Link to item Cite

Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases.

Journal Article J Immunol · March 1983 Thymic epithelium from three patients with severe cellular immunodeficiency diseases were compared with age-matched normal thymic epithelium using three markers of human thymic epithelium and antibodies against thymosin alpha 1, thymopoietin, and thymosin ... Link to item Cite

Identification of human and rodent thymic epithelium using tetanus toxin and monoclonal antibody A2B5.

Journal Article J Clin Invest · January 1983 Using a monoclonal antibody (A2B5), which binds to GQ ganglioside, and tetanus toxin, which binds to GD and GT gangliosides, distinct regions of human and rodent thymic epithelial cells have been identified. The lymphoid elements of the thymus do not bind ... Full text Link to item Cite

Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years.

Journal Article Ann Intern Med · January 1983 Eighty-five patients with Wegener's granulomatosis were studied for 21 years at the National Institutes of Health. Patients were treated with a protocol consisting of cyclophosphamide, 2 mg/kg body weight d, together with prednisone, 1 mg/kg body weight d, ... Full text Link to item Cite

Candidate counterparts of Sézary cells and adult T-cell lymphoma-leukaemia cells in normal peripheral blood: an ultrastructural study with the immunogold method and monoclonal antibodies.

Journal Article Leuk Res · 1983 The ultrastructural and immunologic features of normal convoluted T-lymphocytes were studied with a panel of monoclonal antibodies and the immunogold technique and these were compared with cells from patients with Sézary syndrome (SS) and adult T-cell lymp ... Full text Link to item Cite

Assessing treatments with cyclophosphamide

Journal Article Annals of Internal Medicine · 1983 Cite

ASSESSING TREATMENTS WITH CYCLOPHOSPHAMIDE - COMMENT

Journal Article ANNALS OF INTERNAL MEDICINE · January 1, 1983 Link to item Cite