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

Author

Listed:
  • Jinghe Huang

    (HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Gilad Ofek

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Leo Laub

    (HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Mark K. Louder

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Nicole A. Doria-Rose

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Nancy S. Longo

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Hiromi Imamichi

    (HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Robert T. Bailer

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Bimal Chakrabarti

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute)

  • Shailendra K. Sharma

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute)

  • S. Munir Alam

    (Duke Human Vaccine Institute, Duke University)

  • Tao Wang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Yongping Yang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Baoshan Zhang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Stephen A. Migueles

    (HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Richard Wyatt

    (IAVI Neutralizing Antibody Center, The Scripps Research Institute)

  • Barton F. Haynes

    (Duke Human Vaccine Institute, Duke University)

  • Peter D. Kwong

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • John R. Mascola

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Mark Connors

    (HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

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.

Suggested Citation

  • 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, 2012. "Broad and potent neutralization of HIV-1 by a gp41-specific human antibody," Nature, Nature, vol. 491(7424), pages 406-412, November.
    • Handle: RePEc:nat:nature:v:491:y:2012:i:7424:d:10.1038_nature11544
    DOI: 10.1038/nature11544
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    Cited by:

    1. Nicole A Doria-Rose & Han R Altae-Tran & Ryan S Roark & Stephen D Schmidt & Matthew S Sutton & Mark K Louder & Gwo-Yu Chuang & Robert T Bailer & Valerie Cortez & Rui Kong & Krisha McKee & Sijy O’Dell , 2017. "Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting," PLOS Pathogens, Public Library of Science, vol. 13(1), pages 1-29, January.
    2. Alexander M Sevy & Swetasudha Panda & James E Crowe Jr & Jens Meiler & Yevgeniy Vorobeychik, 2018. "Integrating linear optimization with structural modeling to increase HIV neutralization breadth," PLOS Computational Biology, Public Library of Science, vol. 14(2), pages 1-18, February.
    3. Anna Hake & Nico Pfeifer, 2017. "Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time," PLOS Computational Biology, Public Library of Science, vol. 13(10), pages 1-23, October.

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