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Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.
Antanasijevic, Aleksandar; Sewall, Leigh M; Cottrell, Christopher A; Carnathan, Diane G; Jimenez, Luis E; Ngo, Julia T; Silverman, Jennifer B; Groschel, Bettina; Georgeson, Erik; Bhiman, Jinal; Bastidas, Raiza; LaBranche, Celia; Allen, Joel D; Copps, Jeffrey; Perrett, Hailee R; Rantalainen, Kimmo; Cannac, Fabien; Yang, Yuhe R; de la Peña, Alba Torrents; Rocha, Rebeca Froes; Berndsen, Zachary T; Baker, David; King, Neil P; Sanders, Rogier W; Moore, John P; Crotty, Shane; Crispin, Max; Montefiori, David C; Burton, Dennis R; Schief, William R; Silvestri, Guido; Ward, Andrew B.
Afiliação
  • Antanasijevic A; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Sewall LM; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Cottrell CA; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Carnathan DG; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Jimenez LE; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Ngo JT; International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Silverman JB; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Groschel B; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Georgeson E; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Bhiman J; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Bastidas R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • LaBranche C; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Allen JD; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Copps J; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Perrett HR; Department of Surgery, Duke University Medical Center, Durham, NC, USA.
  • Rantalainen K; School of Biological Sciences, University of Southampton, Southampton, UK.
  • Cannac F; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Yang YR; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • de la Peña AT; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Rocha RF; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Berndsen ZT; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Baker D; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • King NP; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Sanders RW; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Moore JP; Institute for Protein Design, Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Crotty S; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • Crispin M; Institute for Protein Design, Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Montefiori DC; Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.
  • Burton DR; Weill Cornell Medicine, Cornell University, New York, NY, USA.
  • Schief WR; Weill Cornell Medicine, Cornell University, New York, NY, USA.
  • Silvestri G; La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Ward AB; School of Biological Sciences, University of Southampton, Southampton, UK.
Nat Commun ; 12(1): 4817, 2021 08 10.
Article em En | MEDLINE | ID: mdl-34376662
ABSTRACT
Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Vacinas contra a AIDS / Produtos do Gene env do Vírus da Imunodeficiência Humana / Anticorpos Neutralizantes / Anticorpos Monoclonais / Formação de Anticorpos Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Vacinas contra a AIDS / Produtos do Gene env do Vírus da Imunodeficiência Humana / Anticorpos Neutralizantes / Anticorpos Monoclonais / Formação de Anticorpos Idioma: En Ano de publicação: 2021 Tipo de documento: Article