Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.
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.
Huang, J; Ofek, G; Laub, L; Louder, MK; Doria-Rose, NA; Longo, NS; Imamichi, H; Bailer, RT; Chakrabarti, B; Sharma, SK; Alam, SM; Wang, T; Yang, Y; Zhang, B; Migueles, SA; Wyatt, R; Haynes, BF; Kwong, PD; Mascola, JR; Connors, M
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