Author:
Zhao Fangzhu,Berndsen Zachary T.,Pedreño-Lopez Nuria,Burns Alison,Allen Joel D.,Barman Shawn,Lee Wen-Hsin,Chakraborty Srirupa,Gnanakaran Sandrasegaram,Sewall Leigh M.,Ozorowski Gabriel,Limbo Oliver,Song Ge,Yong Peter,Callaghan Sean,Weisgrau Kim L.,Lifson Jeffrey D.,Nedellec Rebecca,Voigt Thomas B,Laurino Fernanda,Louw Johan,Rosen Brandon C.,Ricciardi Michael,Crispin Max,Desrosiers Ronald C.,Rakasz Eva G.,Watkins David I.,Andrabi Raiees,Ward Andrew B.,Burton Dennis R.,Sok Devin
Abstract
SUMMARYSIVmac239 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 low dose intraveneous 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.
Publisher
Cold Spring Harbor Laboratory