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

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 Ozorowski, Oliver Limbo, Ge Song, Peter Yong, Sean Callaghan, Jessica Coppola, Kim L. Weisgrau, Jeffrey D. Lifson, Rebecca Nedellec, Thomas B. Voigt, Fernanda Laurino, Johan Louw, Brandon C. Rosen, Michael Ricciardi, Max Crispin, Ronald C. Desrosiers, Eva G. Rakasz, David I. Watkins, Raiees Andrabi (), Andrew B. Ward (), Dennis R. Burton () and Devin Sok ()
Additional contact information
Fangzhu Zhao: The Scripps Research Institute
Zachary T. Berndsen: The Scripps Research Institute
Nuria Pedreño-Lopez: George Washington University
Alison Burns: The Scripps Research Institute
Joel D. Allen: University of Southampton
Shawn Barman: The Scripps Research Institute
Wen-Hsin Lee: The Scripps Research Institute
Srirupa Chakraborty: Los Alamos National Laboratory
Sandrasegaram Gnanakaran: Los Alamos National Laboratory
Leigh M. Sewall: The Scripps Research Institute
Gabriel Ozorowski: The Scripps Research Institute
Oliver Limbo: The Scripps Research Institute
Ge Song: The Scripps Research Institute
Peter Yong: The Scripps Research Institute
Sean Callaghan: The Scripps Research Institute
Jessica Coppola: 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
Thomas B. Voigt: George Washington University
Fernanda Laurino: George Washington University
Johan Louw: George Washington University
Brandon C. Rosen: George Washington University
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
Andrew B. Ward: The Scripps Research Institute
Dennis R. Burton: The Scripps Research Institute
Devin Sok: The Scripps Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32783-2

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DOI: 10.1038/s41467-022-32783-2

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