Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
Jinghe Huang, Gilad Ofek, Leo Laub, Mark K Louder, Nicole A Doria-Rose, Nancy S Longo, Hiromi Imamichi, Robert T Bailer, Bimal Chakrabarti, Shailendra K Sharma, S Munir Alam, Tao Wang, Yongping Yang, Baoshan Zhang, Stephen A Migueles, Richard Wyatt, Barton F Haynes, Peter D Kwong, John R Mascola, Mark Connors, Jinghe Huang, Gilad Ofek, Leo Laub, Mark K Louder, Nicole A Doria-Rose, Nancy S Longo, Hiromi Imamichi, Robert T Bailer, Bimal Chakrabarti, Shailendra K Sharma, S Munir Alam, Tao Wang, Yongping Yang, Baoshan Zhang, Stephen A Migueles, Richard Wyatt, Barton F Haynes, Peter D Kwong, John R Mascola, Mark Connors
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.
Conflict of interest statement
Competing financial interests The authors declare no competing financial interests.
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References
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