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

机译：gp41特异性人类抗体广泛有效地中和HIV-1

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摘要

Jinghe Huang等人报告了来自一个被HIV-1感rn染的健康供者的一种新颖的中和抗体，它是专rn门针对gp41的膜近侧区的。该抗体有很强效rn力和作用范围，不是自体反应性的，不与磷rn脂结合。这项工作显示了一个具有gp41脆弱rn性的保守点，它是HIV中和的一个重要目标抗rn原，对于试图用疫苗引出具有广泛中和作用的rn抗体的工作有参考意义。%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.
机译：Jinghe Huang等人报告了来自一个被HIV-1感rn染的健康供者的一种新颖的中和抗体，它是专rn门针对gp41的膜近侧区的。该抗体有很强效rn力和作用范围，不是自体反应性的，不与磷rn脂结合。这项工作显示了一个具有gp41脆弱rn性的保守点，它是HIV中和的一个重要目标抗rn原，对于试图用疫苗引出具有广泛中和作用的rn抗体的工作有参考意义。%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.

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  • 来源
    《Nature》 |2012年第7424期|p.406-412a3|共8页
  • 作者

    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;

  • 作者单位

    HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA,These authors contributed equally to this work;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA,These authors contributed equally to this work;

    HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    IAVI Neutralizing Antibody Center, The Scripps Research Institute, Department of Immunology and Microbial Sciences, La Jolla, California 92037, USA;

    IAVI Neutralizing Antibody Center, The Scripps Research Institute, Department of Immunology and Microbial Sciences, La Jolla, California 92037, USA;

    Duke Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    IAVI Neutralizing Antibody Center, The Scripps Research Institute, Department of Immunology and Microbial Sciences, La Jolla, California 92037, USA;

    Duke Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

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