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Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM

Author

Listed:
  • Aleksandar Antanasijevic

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Leigh M. Sewall

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Christopher A. Cottrell

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Diane G. Carnathan

    (Emory University)

  • Luis E. Jimenez

    (Emory University)

  • Julia T. Ngo

    (Emory University)

  • Jennifer B. Silverman

    (Emory University)

  • Bettina Groschel

    (The Scripps Research Institute)

  • Erik Georgeson

    (The Scripps Research Institute)

  • Jinal Bhiman

    (The Scripps Research Institute)

  • Raiza Bastidas

    (The Scripps Research Institute)

  • Celia LaBranche

    (Duke University Medical Center)

  • Joel D. Allen

    (University of Southampton)

  • Jeffrey Copps

    (The Scripps Research Institute)

  • Hailee R. Perrett

    (The Scripps Research Institute)

  • Kimmo Rantalainen

    (The Scripps Research Institute)

  • Fabien Cannac

    (The Scripps Research Institute)

  • Yuhe R. Yang

    (The Scripps Research Institute)

  • Alba Torrents Peña

    (The Scripps Research Institute)

  • Rebeca Froes Rocha

    (The Scripps Research Institute)

  • Zachary T. Berndsen

    (The Scripps Research Institute)

  • David Baker

    (University of Washington
    Howard Hughes Medical Institute)

  • Neil P. King

    (University of Washington)

  • Rogier W. Sanders

    (University of Amsterdam
    Weill Cornell Medicine, Cornell University)

  • John P. Moore

    (Weill Cornell Medicine, Cornell University)

  • Shane Crotty

    (La Jolla Institute for Immunology)

  • Max Crispin

    (University of Southampton)

  • David C. Montefiori

    (Duke University Medical Center)

  • Dennis R. Burton

    (The Scripps Research Institute
    The Scripps Research Institute)

  • William R. Schief

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Guido Silvestri

    (Emory University)

  • Andrew B. Ward

    (The Scripps Research Institute
    The Scripps Research Institute)

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.

Suggested Citation

  • Aleksandar Antanasijevic & Leigh M. Sewall & Christopher A. Cottrell & Diane G. Carnathan & Luis E. Jimenez & Julia T. Ngo & Jennifer B. Silverman & Bettina Groschel & Erik Georgeson & Jinal Bhiman & , 2021. "Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25087-4
    DOI: 10.1038/s41467-021-25087-4
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    Cited by:

    1. Yi-Nan Zhang & Jennifer Paynter & Aleksandar Antanasijevic & Joel D. Allen & Mor Eldad & Yi-Zong Lee & Jeffrey Copps & Maddy L. Newby & Linling He & Deborah Chavez & Pat Frost & Anna Goodroe & John Du, 2023. "Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates," Nature Communications, Nature, vol. 14(1), pages 1-29, December.
    2. Ching-Lin Hsieh & Sarah R. Leist & Emily Happy Miller & Ling Zhou & John M. Powers & Alexandra L. Tse & Albert Wang & Ande West & Mark R. Zweigart & Jonathan C. Schisler & Rohit K. Jangra & Kartik Cha, 2024. "Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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