1. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
- Author
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Huang, Jinghe, Ofek, Gilad, Laub, Leo, Louder, Mark K., Doria-Rose, Nicole A., Longo, Nancy S., Imamichi, Hiromi, Bailer, Robert T., Chakrabarti, Bimal, Sharma, Shailendra K., Alam, S. Munir, Wang, Tao, Yang, Yongping, Zhang, Baoshan, Migueles, Stephen A., Wyatt, Richard, Haynes, Barton F., Kwong, Peter D., Mascola, John R., and Connors, Mark
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Viral antibodies -- Properties -- Research ,Vaccines -- Research ,Antibodies -- Properties -- Research ,HIV infection -- Prevention -- Research ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - 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., Induction of an antibody response capable of neutralizing diverse HIV-1 isolates is a critical goal for vaccines that protect against HIV-1 infection. Potentially the greatest obstacle to achieving this goal [...]
- Published
- 2012
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