Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.

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TitleBroad and potent neutralization of HIV-1 by a gp41-specific human antibody.
Publication TypeJournal Article
Year of Publication2012
AuthorsHuang, J, Ofek, GA, Laub, L, Louder, MK, Doria-Rose, NA, Longo, NS, Imamichi, H, Bailer, RT, Chakrabarti, B, Sharma, SK, S Alam, M, Wang, T, Yang, Y, Zhang, B, Migueles, SA, Wyatt, R, Haynes, BF, Kwong, PD, Mascola, JR, Connors, M
JournalNature
Volume491
Issue7424
Pagination406-12
Date Published2012 Nov 15
ISSN1476-4687
KeywordsAmino Acid Substitution, Antibodies, Neutralizing, Antibody Specificity, Cells, Cultured, HEK293 Cells, HIV Antibodies, HIV Envelope Protein gp41, HIV-1, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Tertiary
Abstract

Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.

DOI10.1038/nature11544
Alternate JournalNature
PubMed ID23151583
Grant ListHSN261200800001E / / PHS HHS / United States
/ / Intramural NIH HHS / United States