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Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins

Author

Listed:
  • Daniëla Maria Hinke

    (University of Oslo
    University of Oslo and Oslo University Hospital)

  • Ane Marie Anderson

    (University of Oslo
    University of Oslo and Oslo University Hospital)

  • Kirankumar Katta

    (University of Oslo and Oslo University Hospital)

  • Marlene Fyrstenberg Laursen

    (University of Oslo and Oslo University Hospital)

  • Demo Yemane Tesfaye

    (University of Oslo and Oslo University Hospital)

  • Ina Charlotta Werninghaus

    (University of Oslo and Oslo University Hospital)

  • Davide Angeletti

    (University of Gothenburg)

  • Gunnveig Grødeland

    (University of Oslo
    University of Oslo and Oslo University Hospital)

  • Bjarne Bogen

    (University of Oslo
    University of Oslo and Oslo University Hospital)

  • Ranveig Braathen

    (University of Oslo
    University of Oslo and Oslo University Hospital)

Abstract

Conserved epitopes shared between virus subtypes are often subdominant, making it difficult to induce broadly reactive antibodies by immunization. Here, we generate a plasmid DNA mix vaccine that encodes protein heterodimers with sixteen different influenza A virus hemagglutinins (HA) representing all HA subtypes except H1 (group 1) and H7 (group 2). Each single heterodimer expresses two different HA subtypes and is targeted to MHC class II on antigen presenting cells (APC). Female mice immunized with the plasmid mix produce antibodies not only against the 16 HA subtypes, but also against non-included H1 and H7. We demonstrate that individual antibody molecules cross-react between different HAs. Furthermore, the mix vaccine induces T cell responses to conserved HA epitopes. Immunized mice are partially protected against H1 viruses. The results show that application of valency-based immuno-selection to diversified antigens can be used to direct antibody responses towards conserved (subdominant) epitopes on viral antigens.

Suggested Citation

  • Daniëla Maria Hinke & Ane Marie Anderson & Kirankumar Katta & Marlene Fyrstenberg Laursen & Demo Yemane Tesfaye & Ina Charlotta Werninghaus & Davide Angeletti & Gunnveig Grødeland & Bjarne Bogen & Ran, 2024. "Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44889-w
    DOI: 10.1038/s41467-024-44889-w
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    References listed on IDEAS

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    1. Jenna J. Guthmiller & Julianna Han & Henry A. Utset & Lei Li & Linda Yu-Ling Lan & Carole Henry & Christopher T. Stamper & Meagan McMahon & George O’Dell & Monica L. Fernández-Quintero & Alec W. Freyn, 2022. "Broadly neutralizing antibodies target a haemagglutinin anchor epitope," Nature, Nature, vol. 602(7896), pages 314-320, February.
    2. Michael B. Doud & Juhye M. Lee & Jesse D. Bloom, 2018. "How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
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