Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth
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 Hraber, Kshitij Wagh, Elena E. Giorgi, Ronnie M. Russell, Frédéric Bibollet‐Ruche, Weimin Liu, Andrew Connell, Andrew G. Smith, Julia C. DeVoto, Alexander I. Murphy, Jessica G. Smith, Wenge Ding, Chengyan Zhao, Neha Chohan, Maho Okumura, Christina Rosario, Yu Ding, Emily Lindemuth, Anya M. Bauer, Katharine J. Bar, David R. Ambrozak, Cara W. Chao, Gwo‐Yu Chuang, Hui Geng, Bob C. Lin, Mark K. Louder, Richard Nguyen, Baoshan Zhang, Mark G. Lewis, D.D. Raymond, Nicole A. Doria‐Rose, Chaim A. Schramm, Daniel C. Douek, Mario Roederer, Thomas B. Kepler, Garnett Kelsoe, John R. Mascola, Peter D. Kwong, Bette Korber, Stephen C. Harrison, Barton F. Haynes, Beatrice H. Hahn, George M. Shaw
Abstract
Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses in rhesus macaques-elicited patterns of Env-antibody coevolution very similar to those in humans, including 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 broadly neutralizing antibodies (bNAbs) PGT145 and PCT64-35S. Another rhesus antibody bound the CD4 binding site by CD4 mimicry, mirroring human bNAbs 8ANC131, CH235, and VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.