HIV envelope glycoform heterogeneity and localized diversity govern the initiation and maturation of a V2 apex broadly neutralizing antibody lineage.

Authors: Landais, Elise and Murrell, Ben and Briney, Bryan and Murrell, Sasha and Rantalainen, Kimmo and Berndsen, Zachary T and Ramos, Alejandra and Wickramasinghe, Lalinda and Smith, Melissa Laird and Eren, Kemal and de Val, Natalia and Wu, Mengyu and Cappelletti, Audrey and Umotoy, Jeffrey and Lie, Yolanda and Wrin, Terri and Algate, Paul and Chan-Hui, Po-Ying and Karita, Etienne and Ward, Andrew B and Wilson, Ian A and Burton, Dennis R and Smith, Davey and Pond, Sergei L Kosakovsky and Poignard, Pascal

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. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Journal: Immunity
DOI: 10.1016/j.immuni.2017.11.002
Year: 2017

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