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Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate

Author

Listed:
  • Kwinten Sliepen

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Laura Radić

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Joan Capella-Pujol

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Yasunori Watanabe

    (University of Southampton)

  • Ian Zon

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Ana Chumbe

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Wen-Hsin Lee

    (The Scripps Research Institute)

  • Marlon Gast

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Jelle Koopsen

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Sylvie Koekkoek

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Iván Moral-Sánchez

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Philip J. M. Brouwer

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Rashmi Ravichandran

    (University of Washington
    University of Washington)

  • Gabriel Ozorowski

    (The Scripps Research Institute)

  • Neil P. King

    (University of Washington
    University of Washington)

  • Andrew B. Ward

    (The Scripps Research Institute)

  • Marit J. Gils

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Max Crispin

    (University of Southampton)

  • Janke Schinkel

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases)

  • Rogier W. Sanders

    (Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
    Amsterdam Institute for Infection and Immunity, Infectious Diseases
    Weill Medical College of Cornell University)

Abstract

Hepatitis C virus (HCV) infection affects approximately 58 million people and causes ~300,000 deaths yearly. The only target for HCV neutralizing antibodies is the highly sequence diverse E1E2 glycoprotein. Eliciting broadly neutralizing antibodies that recognize conserved cross-neutralizing epitopes is important for an effective HCV vaccine. However, most recombinant HCV glycoprotein vaccines, which usually include only E2, induce only weak neutralizing antibody responses. Here, we describe recombinant soluble E1E2 immunogens that were generated by permutation of the E1 and E2 subunits. We displayed the E2E1 immunogens on two-component nanoparticles and these nanoparticles induce significantly more potent neutralizing antibody responses than E2. Next, we generated mosaic nanoparticles co-displaying six different E2E1 immunogens. These mosaic E2E1 nanoparticles elicit significantly improved neutralization compared to monovalent E2E1 nanoparticles. These results provide a roadmap for the generation of an HCV vaccine that induces potent and broad neutralization.

Suggested Citation

  • Kwinten Sliepen & Laura Radić & Joan Capella-Pujol & Yasunori Watanabe & Ian Zon & Ana Chumbe & Wen-Hsin Lee & Marlon Gast & Jelle Koopsen & Sylvie Koekkoek & Iván Moral-Sánchez & Philip J. M. Brouwer, 2022. "Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34961-8
    DOI: 10.1038/s41467-022-34961-8
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    References listed on IDEAS

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    Cited by:

    1. 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.

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