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Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus

Author

Listed:
  • Fangzhu Zhao

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Zachary T. Berndsen

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Nuria Pedreño-Lopez

    (George Washington University)

  • Alison Burns

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Joel D. Allen

    (University of Southampton)

  • Shawn Barman

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Wen-Hsin Lee

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Srirupa Chakraborty

    (Los Alamos National Laboratory)

  • Sandrasegaram Gnanakaran

    (Los Alamos National Laboratory)

  • Leigh M. Sewall

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Gabriel Ozorowski

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Oliver Limbo

    (The Scripps Research Institute
    IAVI)

  • Ge Song

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Peter Yong

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Sean Callaghan

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Jessica Coppola

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Kim L. Weisgrau

    (University of Wisconsin-Madison)

  • Jeffrey D. Lifson

    (Frederick National Laboratory for Cancer Research)

  • Rebecca Nedellec

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Thomas B. Voigt

    (George Washington University)

  • Fernanda Laurino

    (George Washington University)

  • Johan Louw

    (George Washington University)

  • Brandon C. Rosen

    (George Washington University
    Miller School of Medicine, University of Miami)

  • Michael Ricciardi

    (George Washington University)

  • Max Crispin

    (University of Southampton)

  • Ronald C. Desrosiers

    (Miller School of Medicine, University of Miami)

  • Eva G. Rakasz

    (University of Wisconsin-Madison)

  • David I. Watkins

    (George Washington University)

  • Raiees Andrabi

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Dennis R. Burton

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute
    Massachusetts Institute of Technology, and Harvard University)

  • Devin Sok

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute
    IAVI)

Abstract

SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.

Suggested Citation

  • Fangzhu Zhao & Zachary T. Berndsen & Nuria Pedreño-Lopez & Alison Burns & Joel D. Allen & Shawn Barman & Wen-Hsin Lee & Srirupa Chakraborty & Sandrasegaram Gnanakaran & Leigh M. Sewall & Gabriel Ozoro, 2022. "Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32783-2
    DOI: 10.1038/s41467-022-32783-2
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    References listed on IDEAS

    as
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