HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage.

TitleHIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage.
Publication TypeJournal Article
Year of Publication2017
AuthorsLandais E, Murrell B, Briney B, Murrell S, Rantalainen K, Berndsen ZT, Ramos A, Wickramasinghe L, Smith MLaird, Eren K, de Val N, Wu M, Cappelletti A, Umotoy J, Lie Y, Wrin T, Algate P, Chan-Hui P-Y, Karita E, Ward AB, Wilson IA, Burton DR, Smith D, Pond SLKosakovs, Poignard P
Corporate AuthorsIAVI Protocol C Investigators, IAVI African HIV Research Network
JournalImmunity
Volume47
Issue5
Pagination990-1003.e9
Date Published11/21/2017
ISSN1097-4180
KeywordsAIDS Vaccines, Antibodies, Neutralizing, Cell Lineage, Complementarity Determining Regions, env Gene Products, Human Immunodeficiency Virus, HIV Antibodies, Humans
Abstract

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.

DOI10.1016/j.immuni.2017.11.002
Alternate JournalImmunity
PubMed ID29166592
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
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