Kavli Affiliate: Robert Edwards
| Authors: Matthew Clark, Hui Li, Mitchell Martin, Tyler Evangelous, Sophie Gobeil, Madison Berry, Kshitij Wagh, Elena Giorgi, Michael Hogarty, Chengyan Zhao, Shuyi Wang, Lorie Marchitto, Wenge Ding, Younghoon Park, Juliette Rando, John Carey, Andrew Connell, Ashwin Skelly, Yue Chen, Seth Rohr, Chuancang Jiang, Sravani Venkatayogi, Katayoun Mansouri, Robert J. Edwards, Jared Lindenberger, Bhavna Hora, Nicole A Doria-Rose, John Mascola, Marit J van Gils, Rogier W. Sanders, Bette Korber, Beatrice H Hahn, Kevin O’Neil Saunders, Priyamvada Acharya, Kevin Wiehe, Barton F. Haynes, George M Shaw and Wilton B Williams
| Summary:
Understanding broadly neutralizing antibody (bnAb) lineage development in rhesus macaques (RMs) infected with Simian-HIV (SHIV) may inform HIV-1 vaccine designs. We analyzed HIV-1 envelope-antibody coevolution in 18 RMs infected by SHIV.BG505 (subtype A) and found highly conserved patterns of antibody recognition and Env escape, including in three animals that developed V3-glycan bnAbs. From one RM with V3-glycan targeted plasma breadth, we isolated 203 members of a single clonal Ab lineage designated DH1030. DH1030 Abs demonstrated striking genetic, functional and structural similarities with the human V3-glycan bnAb lineage DH270, which was isolated from an individual with subtype C HIV-1 CH848 infection. Notably, human-DH270 and macaque-DH1030 bnAbs shared early improbable mutations in HCDR2 that were critical for bnAb development. Thus, key improbable mutations and convergent patterns of antibody evolution and epitope recognition were shared across primate species and distinct HIV-1 subtypes, findings that may be leveraged in new HIV-1 vaccine designs. ONE SENTENCE SUMMARY Broadly neutralizing antibodies targeting HIV-1 envelope surface protein develop via a common maturation pathway across primate phylogeny.