Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design.

TitleCo-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design.
Publication TypeJournal Article
Year of Publication2018
AuthorsRantalainen K, Berndsen ZT, Murrell S, Cao L, Omorodion O, Torres JL, Wu M, Umotoy J, Copps J, Poignard P, Landais E, Paulson JC, Wilson IA, Ward AB
JournalCell Rep
Volume23
Issue11
Pagination3249-3261
Date Published06/12/2018
ISSN2211-1247
Abstract

Broadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at serial time points during infection provide a basis for understanding the co-evolutionary contest between HIV and the humoral immune system. Here, we describe the structural characterization of an apex-targeting antibody lineage and autologous clade A viral Env from a donor in the Protocol C cohort. Comparison of Ab-Env complexes at early and late time points reveals that, within the antibody lineage, the CDRH3 loop rigidifies, the bnAb angle of approach steepens, and surface charges are mutated to accommodate glycan changes. Additionally, we observed differences in site-specific glycosylation between soluble and full-length Env constructs, which may be important for tuning optimal immunogenicity in soluble Env trimers. These studies therefore provide important guideposts for design of immunogens that prime and mature nAb responses to the Env V2-apex.

DOI10.1016/j.celrep.2018.05.046
Alternate JournalCell Rep
PubMed ID29898396
PubMed Central IDPMC6019700
Grant ListP41 GM103393 / GM / NIGMS NIH HHS / United States
R01 AI113867 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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