Authors
Matthew Clark, Hui Li, Mitchell Martin, Tyler D Evangelous, Sophie M-C Gobeil, Madison Berry, Kshitij Wagh, Elena E Giorgi, Michael P Hogarty, Chengyan Zhao, Shuyi Wang, Lorie Marchitto, Wenge Ding, Younghoon Park, Juliette Rando, John Carey, Andrew J Connell, Ashwin N Skelly, Yue Chen, Seth Rohr, Samantha Balgobin, Chuancang Jiang, Sravani Venkatayogi, Katayoun Mansouri, Robert J Edwards, Jared Lindenberger, Bhavna Hora, Nicole Doria-Rose, John Mascola, Marit J van Gils, Rogier W Sanders, Bette Korber, Beatrice Hahn, Kevin O Saunders, Priyamvada Acharya, Kevin Wiehe, Barton F Haynes, George M Shaw, Wilton B Williams
Published in
Science translational medicine. Volume 18. Issue 857. Pages eaee9864. Jul 08, 2026. Epub Jul 08, 2026.
Abstract
Understanding broadly neutralizing antibody (bnAb) lineage development in rhesus macaques (RMs) infected with simian-human immunodeficiency virus (SHIV) may inform HIV-1 vaccine designs. We analyzed HIV-1 envelope (Env)-antibody coevolution in 18 RMs infected with SHIV.BG505 (subtype A) and found conserved patterns of antibody recognition and Env escape, including in three animals that developed V3-glycan-reactive bnAbs. From one RM with V3-glycan-targeted plasma Abs that neutralized heterologous HIV-1 strains, we isolated 203 members of a single clonal antibody lineage designated DH1030. DH1030 antibodies demonstrated 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. Human-DH270 and macaque-DH1030 bnAbs shared early improbable mutations in the heavy chain complementarity determining region 2 that were critical for bnAb development. These convergent patterns of antibody evolution, accumulation of key improbable mutations, and mode of epitope recognition were shared across primate species and distinct HIV-1 subtypes, findings that may be leveraged in HIV-1 vaccine designs. Furthermore, our data highlight the value of SHIV-infected macaques as an outbred model system to explore conserved molecular pathways of bnAb development after infection and vaccination.
PMID:
42418555
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.
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