ジャーナル: Immunity / 年: 2017 タイトル: HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage. 著者: Elise Landais / Ben Murrell / Bryan Briney / Sasha Murrell / Kimmo Rantalainen / Zachary T Berndsen / Alejandra Ramos / Lalinda Wickramasinghe / Melissa Laird Smith / Kemal Eren / Natalia de ...著者: Elise Landais / Ben Murrell / Bryan Briney / Sasha Murrell / Kimmo Rantalainen / Zachary T Berndsen / Alejandra Ramos / Lalinda Wickramasinghe / Melissa Laird Smith / Kemal Eren / Natalia de Val / Mengyu Wu / Audrey Cappelletti / Jeffrey Umotoy / Yolanda Lie / Terri Wrin / Paul Algate / Po-Ying Chan-Hui / Etienne Karita / / / Andrew B Ward / Ian A Wilson / Dennis R Burton / Davey Smith / Sergei L Kosakovsky Pond / Pascal Poignard / 要旨: Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb ...Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design.