National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1 AI144462
米国
Bill & Melinda Gates Foundation
OPP1196345/INV-008813
米国
引用
ジャーナル: Nat Commun / 年: 2022 タイトル: Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus. 著者: 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 / ...著者: 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 / Devin Sok / 要旨: 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 ...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.