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Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein

Author

Listed:
  • Jelle Schooten

    (University of Amsterdam)

  • Elinaz Farokhi

    (The Scripps Research Institute)

  • Anna Schorcht

    (University of Amsterdam)

  • Tom L. G. M. Kerkhof

    (University of Amsterdam)

  • Hongmei Gao

    (Duke University Medical Center)

  • Patricia Woude

    (University of Amsterdam)

  • Judith A. Burger

    (University of Amsterdam)

  • Tim G. Rijkhold Meesters

    (University of Amsterdam)

  • Tom Bijl

    (University of Amsterdam)

  • Riham Ghalaiyini

    (University of Amsterdam)

  • Hannah L. Turner

    (The Scripps Research Institute)

  • Jessica Dorning

    (Harvard Medical School)

  • Barbera D. C. Schaik

    (University of Amsterdam)

  • Antoine H. C. Kampen

    (University of Amsterdam)

  • Celia C. Labranche

    (Duke University Medical Center)

  • Robyn L. Stanfield

    (The Scripps Research Institute)

  • Devin Sok

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute
    International AIDS Vaccine Initiative)

  • David C. Montefiori

    (Duke University Medical Center)

  • Dennis R. Burton

    (The Scripps Research Institute
    The Scripps Research Institute
    International AIDS Vaccine Initiative
    Ragon Institute of MGH, MIT and Harvard)

  • Michael S. Seaman

    (Harvard Medical School)

  • Gabriel Ozorowski

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Ian A. Wilson

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Rogier W. Sanders

    (University of Amsterdam
    Weill Medical College of Cornell University)

  • Andrew B. Ward

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Marit J. Gils

    (University of Amsterdam)

Abstract

A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2-derived VRC01-class bNAbs, it does not require a rare short light chain complementarity-determining region 3 (CDRL3). Here, we describe three IOMA-class NAbs, ACS101-103, with up to 37% breadth, that share many characteristics with IOMA, including an average-length CDRL3. Cryo-electron microscopy revealed that ACS101 shares interactions with those observed with other VH1-2 and VH1-46-class bNAbs, but exhibits a unique binding mode to residues in loop D. Analysis of longitudinal sequences from the patient suggests that a transmitter/founder-virus lacking the N276 glycan might have initiated the development of these NAbs. Together these data strengthen the rationale for germline-targeting vaccination strategies to induce IOMA-class bNAbs and provide a wealth of sequence and structural information to support such strategies.

Suggested Citation

  • Jelle Schooten & Elinaz Farokhi & Anna Schorcht & Tom L. G. M. Kerkhof & Hongmei Gao & Patricia Woude & Judith A. Burger & Tim G. Rijkhold Meesters & Tom Bijl & Riham Ghalaiyini & Hannah L. Turner & J, 2022. "Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32208-0
    DOI: 10.1038/s41467-022-32208-0
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    References listed on IDEAS

    as
    1. Kwinten Sliepen & Byung Woo Han & Ilja Bontjer & Petra Mooij & Fernando Garces & Anna-Janina Behrens & Kimmo Rantalainen & Sonu Kumar & Anita Sarkar & Philip J. M. Brouwer & Yuanzi Hua & Monica Tolazz, 2019. "Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
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