Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth
By
Ryan S Roark,
Hui Li,
Wilton B Williams,
Hema Chug,
Rosemarie D. Mason,
Jason Gorman,
Shuyi Wang,
Fang-Hua Lee,
Juliette Rando,
Mattia Bonsignori,
Kwan-Ki Hwang,
Kevin O Saunders,
Kevin Wiehe,
M Anthony Moody,
Peter T Hraber,
Kshitij Wagh,
Elena E. Giorgi,
Ronnie M Russell,
Frederic Bibollet-Ruche,
Weimin Liu,
Jesse Connell,
Andrew G Smith,
Julia DeVoto,
Alexander I Murphy,
Jessica Smith,
Wenge Ding,
Chengyan Zhao,
Neha Chohan,
Maho Okumura,
Christina Rosario,
Yu Ding,
Emily Lindemuth,
Anya M Bauer,
Katharine J Bar,
David Ambrozak,
Cara W. Chao,
Gwo-Yu Chuang,
Hui Geng,
Bob C Lin,
Mark K. Louder,
Richard Nguyen,
Baoshan Zhang,
Mark G Lewis,
Donald Raymond,
Nicole A. Doria-Rose,
Chaim A Schramm,
Daniel C Douek,
Mario Roederer,
Thomas B. Kepler,
Garnett Kelsoe,
John R. Mascola,
Peter D. Kwong,
B Korber,
Stephen C. Harrison,
Barton F Haynes,
Beatrice H. Hahn,
George M Shaw
Posted 05 Aug 2020
bioRxiv DOI: 10.1101/2020.08.05.237693
(published DOI: 10.1126/science.abd2638)
Neutralizing antibodies elicited by HIV-1 coevolve with viral Envs in distinctive patterns, in some cases acquiring substantial breadth. Here we show that primary HIV-1 Envs, when expressed by simian-human immunodeficiency viruses in rhesus macaques, elicited patterns of Env-antibody coevolution strikingly similar to those in humans. This included conserved immunogenetic, structural and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2-apex mode of recognition like that of human bNAbs PGT145/PCT64-35M. Another rhesus antibody bound the CD4-binding site by CD4 mimicry mirroring human bNAbs 8ANC131/CH235/VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design. ### Competing Interest Statement The authors have declared no competing interest.
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