Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein

A new method is used to isolate neutralizing antibodies recognizing a new epitope on the cell surface–expressed, but not soluble, HIV-1 spike.

[1]  L. Stamatatos,et al.  Characterization of Neutralizing Antibody Responses Elicited by Clade A Envelope Immunogens Derived from Early Transmitted Viruses , 2008, Journal of Virology.

[2]  J. Mascola,et al.  Protection of Macaques against Pathogenic Simian/Human Immunodeficiency Virus 89.6PD by Passive Transfer of Neutralizing Antibodies , 1999, Journal of Virology.

[3]  Mario Roederer,et al.  Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 , 2010, Science.

[4]  Pham Phung,et al.  Broad neutralization coverage of HIV by multiple highly potent antibodies , 2011, Nature.

[5]  L. Stamatatos,et al.  Binding Interactions between Soluble HIV Envelope Glycoproteins and Quaternary-Structure-Specific Monoclonal Antibodies PG9 and PG16 , 2011, Journal of Virology.

[6]  M. Nussenzweig,et al.  Predominant Autoantibody Production by Early Human B Cell Precursors , 2003, Science.

[7]  Pham Phung,et al.  Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target , 2009, Science.

[8]  L. Stamatatos,et al.  Identification of a New Quaternary Neutralizing Epitope on Human Immunodeficiency Virus Type 1 Virus Particles , 2005, Journal of Virology.

[9]  Michel C Nussenzweig,et al.  Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. , 2008, Journal of immunological methods.

[10]  D R Burton,et al.  Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. , 1994, Science.

[11]  Ron Diskin,et al.  Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design , 2011, Science.

[12]  D. Burton,et al.  Broadly Neutralizing Human Anti-HIV Antibody 2G12 Is Effective in Protection against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers , 2009, PLoS pathogens.

[13]  Ron Diskin,et al.  Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding , 2011, Science.

[14]  Richard T. Wyatt,et al.  Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables , 2009, Journal of Virology.

[15]  Martin A. Nowak,et al.  Antibody neutralization and escape by HIV-1 , 2003, Nature.

[16]  Mario Roederer,et al.  Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing , 2011, Science.

[17]  S. Gordon,et al.  Ligands for the β-Glucan Receptor, Dectin-1, Assigned Using “Designer” Microarrays of Oligosaccharide Probes (Neoglycolipids) Generated from Glucan Polysaccharides* , 2006, Journal of Biological Chemistry.

[18]  L. Stamatatos,et al.  Changes in the Immunogenic Properties of Soluble gp140 Human Immunodeficiency Virus Envelope Constructs upon Partial Deletion of the Second Hypervariable Region , 2003, Journal of Virology.

[19]  Yan Liu,et al.  A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield , 2011, Science.

[20]  Persephone Borrow,et al.  The immune response during acute HIV-1 infection: clues for vaccine development , 2009, Nature Reviews Immunology.

[21]  D. Richman,et al.  Rapid evolution of the neutralizing antibody response to HIV type 1 infection , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Hanneke Schuitemaker,et al.  Autologous Neutralizing Humoral Immunity and Evolution of the Viral Envelope in the Course of Subtype B Human Immunodeficiency Virus Type 1 Infection , 2008, Journal of Virology.

[23]  Young Do Kwon,et al.  Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9 , 2011, Nature.

[24]  Pascal Poignard,et al.  Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques , 2009, Nature Medicine.

[25]  L. Morris,et al.  The Neutralization Breadth of HIV-1 Develops Incrementally over Four Years and Is Associated with CD4+ T Cell Decline and High Viral Load during Acute Infection , 2011, Journal of Virology.

[26]  Xuesong Yu,et al.  Factors Associated with the Development of Cross-Reactive Neutralizing Antibodies during Human Immunodeficiency Virus Type 1 Infection , 2008, Journal of Virology.

[27]  M. Nussenzweig,et al.  Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses , 2011, PloS one.

[28]  S. Zolla-Pazner,et al.  Anti-V3 Monoclonal Antibodies Display Broad Neutralizing Activities against Multiple HIV-1 Subtypes , 2009, PloS one.

[29]  Susan Moir,et al.  Prospects for an HIV vaccine: leading B cells down the right path , 2011, Nature Structural &Molecular Biology.

[30]  W. Chai,et al.  Neoglycolipid-based oligosaccharide microarray system: preparation of NGLs and their noncovalent immobilization on nitrocellulose-coated glass slides for microarray analyses. , 2012, Methods in molecular biology.

[31]  Terri Wrin,et al.  Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm , 2009, Journal of Virology.

[32]  J. Albert,et al.  Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. , 1990, AIDS.

[33]  R. Rosenfeld.  Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[34]  T. Kepler,et al.  Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting , 2011, PloS one.

[35]  G Himmler,et al.  A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1 , 1993, Journal of virology.

[36]  David C Montefiori,et al.  The role of antibodies in HIV vaccines. , 2010, Annual review of immunology.

[37]  A. Trkola,et al.  Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies , 2005, Nature Medicine.

[38]  Dennis R. Burton,et al.  A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals , 2010, PLoS pathogens.

[39]  T. Kepler,et al.  Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design , 2012, Journal of Virology.

[40]  F. Pereyra,et al.  A method for identification of HIV gp140 binding memory B cells in human blood. , 2009, Journal of immunological methods.

[41]  Q. Sattentau,et al.  Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals , 2010, PloS one.

[42]  L. Morris,et al.  The Antibody Response against HIV-1. , 2012, Cold Spring Harbor perspectives in medicine.

[43]  L. Stamatatos,et al.  The V1, V2, and V3 Regions of the Human Immunodeficiency Virus Type 1 Envelope Differentially Affect the Viral Phenotype in an Isolate-Dependent Manner , 2005, Journal of Virology.

[44]  Xiping Wei,et al.  Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies , 2005, Journal of Virology.

[45]  Maxim N. Artyomov,et al.  Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation , 2010, Nature.

[46]  Richard T. Wyatt,et al.  Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals , 2009, Nature.

[47]  T. Kepler,et al.  Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors , 2011, Journal of Virology.

[48]  D. Montefiori,et al.  Evaluating Neutralizing Antibodies Against HIV, SIV, and SHIV in Luciferase Reporter Gene Assays , 2004, Current protocols in immunology.

[49]  M. Nussenzweig,et al.  Human anti–HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness , 2010, The Journal of experimental medicine.

[50]  H. Mouquet,et al.  Proteomic analysis of the autoantibody response following immunization with a single autoantigen , 2006, Proteomics.

[51]  A. Trkola,et al.  Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1 , 1996, Journal of virology.

[52]  M. Altfeld,et al.  Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1 , 2011, PLoS pathogens.

[53]  J. Mascola,et al.  Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies , 2000, Nature Medicine.

[54]  Guido Ferrari,et al.  Immune-correlates analysis of an HIV-1 vaccine efficacy trial. , 2012, The New England journal of medicine.

[55]  Lynn Morris,et al.  Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? , 2009, Nature Medicine.

[56]  N. Haigwood,et al.  Neutralizing antibody directed against the HIV–1 envelope glycoprotein can completely block HIV–1/SIV chimeric virus infections of macaque monkeys , 1999, Nature Medicine.

[57]  Holly Janes,et al.  Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies , 2009, Journal of Virology.

[58]  H. Wigzell.  Prospects for an HIV‐vaccine , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[59]  A. Trkola,et al.  A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. , 1994, AIDS research and human retroviruses.