Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike.

TitleAntibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike.
Publication TypeJournal Article
Year of Publication2014
AuthorsScharf L, Scheid JF, Lee J H, West AP, Chen C, Gao H, Gnanapragasam PNP, Mares R, Seaman MS, Ward AB, Nussenzweig MC, Bjorkman PJ
JournalCell Rep
Volume7
Issue3
Pagination785-95
Date Published05/08/2014
ISSN2211-1247
Abstract

Broadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, are currently limited. We defined a new site of vulnerability by solving structures of bNAb 8ANC195 complexed with monomeric gp120 by X-ray crystallography and trimeric Env by electron microscopy. The site includes portions of gp41 and N-linked glycans adjacent to the CD4-binding site on gp120, making 8ANC195 the first donor-derived anti-HIV-1 bNAb with an epitope spanning both Env subunits. Rather than penetrating the glycan shield by using a single variable-region CDR loop, 8ANC195 inserted its entire heavy-chain variable domain into a gap to form a large interface with gp120 glycans and regions of the gp120 inner domain not contacted by other bNAbs. By isolating additional 8ANC195 clonal variants, we identified a more potent variant, which may be valuable for therapeutic approaches using bNAb combinations with nonoverlapping epitopes.

DOI10.1016/j.celrep.2014.04.001
Alternate JournalCell Rep
PubMed ID24767986
Grant List1UM1 AI100663-01 / AI / NIAID NIH HHS / United States
GM103310 / GM / NIGMS NIH HHS / United States
P01 AI082362 / AI / NIAID NIH HHS / United States
P01 AI100148 / AI / NIAID NIH HHS / United States
P01 AI100148 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
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