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Signatures of VH1-69-derived hepatitis C virus neutralizing antibody precursors defined by binding to envelope glycoproteins

Author

Listed:
  • Joan Capella-Pujol

    (University of Amsterdam
    Infectious Diseases)

  • Marlon Gast

    (University of Amsterdam
    Infectious Diseases)

  • Laura Radić

    (University of Amsterdam
    Infectious Diseases)

  • Ian Zon

    (University of Amsterdam
    Infectious Diseases)

  • Ana Chumbe

    (University of Amsterdam
    Infectious Diseases)

  • Sylvie Koekkoek

    (University of Amsterdam
    Infectious Diseases)

  • Wouter Olijhoek

    (University of Amsterdam
    Infectious Diseases)

  • Janke Schinkel

    (University of Amsterdam
    Infectious Diseases)

  • Marit J. Gils

    (University of Amsterdam
    Infectious Diseases)

  • Rogier W. Sanders

    (University of Amsterdam
    Infectious Diseases
    Weill Medical College of Cornell University)

  • Kwinten Sliepen

    (University of Amsterdam
    Infectious Diseases)

Abstract

An effective preventive vaccine for hepatitis C virus (HCV) remains a major unmet need. Antigenic region 3 (AR3) on the E1E2 envelope glycoprotein complex overlaps with the CD81 receptor binding site and represents an important epitope for broadly neutralizing antibodies (bNAbs) and is therefore important for HCV vaccine design. Most AR3 bNAbs utilize the VH1-69 gene and share structural features that define the AR3C-class of HCV bNAbs. In this work, we identify recombinant HCV glycoproteins based on a permuted E2E1 trimer design that bind to the inferred VH1-69 germline precursors of AR3C-class bNAbs. When presented on nanoparticles, these recombinant E2E1 glycoproteins efficiently activate B cells expressing inferred germline AR3C-class bNAb precursors as B cell receptors. Furthermore, we identify critical signatures in three AR3C-class bNAbs that represent two subclasses of AR3C-class bNAbs that will allow refined protein design. These results provide a framework for germline-targeting vaccine design strategies against HCV.

Suggested Citation

  • Joan Capella-Pujol & Marlon Gast & Laura Radić & Ian Zon & Ana Chumbe & Sylvie Koekkoek & Wouter Olijhoek & Janke Schinkel & Marit J. Gils & Rogier W. Sanders & Kwinten Sliepen, 2023. "Signatures of VH1-69-derived hepatitis C virus neutralizing antibody precursors defined by binding to envelope glycoproteins," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39690-0
    DOI: 10.1038/s41467-023-39690-0
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    References listed on IDEAS

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