Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.
Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.
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DOI：
10.1038/nature11544
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发表时间：
2012-11-15
期刊：
影响因子：
64.8
通讯作者：
Connors M
中科院分区：
文献类型：
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作者：
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
人类单抗的特性为广泛的HIV-1中和机制提供了相当大的洞察力。在这里，我们报道了一种HIV-1gp41膜近端外区(MPER)特异性抗体，命名为10E8，它能中和约98%的测试病毒。对78名健康的HIV-1感染者血清的分析表明，27%的人含有MPER特异性抗体，8%的人含有类似10E8的抗体。与其他中和性MPER抗体相比，10E8不结合磷脂，不具有自身反应性，并结合细胞表面被膜。10E8与完整MPER的复合体结构揭示了一个脆弱部位，包括一段高度保守的gp41-疏水残基和紧邻跨膜区之前的关键Arg/Lys。对HIV-1耐药变异体的分析证实了这些残基对中和的重要性。高度保守的MPER是有效的、非自身反应性中和抗体的靶标，这表明HIV-1疫苗应该旨在诱导针对HIV-1Env这一区域的抗体。
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 Arg/Lys just prior to 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 Env.