Authors
Frederic Bibollet-Ruche, Ronnie M Russell, Wenge Ding, Weimin Liu, Yingying Li, Kshitij Wagh, Daniel Wrapp, Rumi Habib, Ashwin N Skelly, Ryan S Roark, Scott Sherrill-Mix, Shuyi Wang, Juliette Rando, Emily Lindemuth, Kendra Cruickshank, Younghoon Park, Rachel Baum, John W Carey, Andrew Jesse Connell, Hui Li, Elena E Giorgi, Ge S Song, Shilei Ding, Andrés Finzi, Amanda Newman, Giovanna E Hernandez, Emily Machiele, Derek W Cain, Katayoun Mansouri, Mark G Lewis, David C Montefiori, Kevin J Wiehe, S Munir Alam, I-Ting Teng, Peter D Kwong, Raiees Andrabi, Laurent Verkoczy, Dennis R Burton, Bette T Korber, Kevin O Saunders, Barton F Haynes, Robert J Edwards, George M Shaw, Beatrice H Hahn
Publication date
2023/2/28
Journal
Mbio
Volume
14
Issue
1
Pages
e03370-22
Publisher
American Society for Microbiology
Description
HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in human V2-apex bNAb heavy-chain precursor-expressing knock-in mice and as chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) in rhesus macaques (RMs). Trimer immunization of knock-in mice induced V2-directed NAbs, indicating activation of V2-apex bNAb precursor-expressing mouse B cells. SCIV infection of RMs elicited high-titer viremia, potent autologous tier 2 neutralizing antibodies, and rapid sequence escape in the canonical V2-apex epitope. Six of seven animals also developed low-titer heterologous plasma breadth that mapped to the V2-apex. Antibody cloning from two of these animals identified multiple expanded lineages with …
Total citations
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