Humans and rhesus macaques share maturation pathways of HIV-1 envelope-reactive V3-glycan bnAb lineages.
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Clark Matthew, Li Hui, Martin Mitchell, Evangelous Tyler D, Gobeil Sophie M-C, Berry Madison, Wagh Kshitij, Giorgi Elena E, Hogarty Michael P, Zhao Chengyan, Wang Shuyi, Marchitto Lorie, Ding Wenge, Park Younghoon, Rando Juliette, Carey John, Connell Andrew J, Skelly Ashwin N, Chen Yue, Rohr Seth, Balgobin Samantha, Jiang Chuancang, Venkatayogi Sravani, Mansouri Katayoun, Edwards Robert J, Lindenberger Jared, Hora Bhavna, Doria-Rose Nicole, Mascola John, van Gils Marit J, Sanders Rogier W, Korber Bette, Hahn Beatrice, Saunders Kevin O, Acharya Priyamvada, Wiehe Kevin, Haynes Barton F, Shaw George M, Williams Wilton B
Аннотация
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.