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Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

Author

Listed:
  • A. Brenda Kapingidza

    (Duke University
    Duke University)

  • Daniel J. Marston

    (Duke University
    Duke University)

  • Caitlin Harris

    (Duke University
    Duke University)

  • Daniel Wrapp

    (Duke University
    Duke University)

  • Kaitlyn Winters

    (Duke University
    Duke University)

  • Dieter Mielke

    (Duke University
    Duke University)

  • Lu Xiaozhi

    (Duke University
    Duke University)

  • Qi Yin

    (Duke University
    Duke University)

  • Andrew Foulger

    (Duke University
    Duke University)

  • Rob Parks

    (Duke University
    Duke University)

  • Maggie Barr

    (Duke University
    Duke University)

  • Amanda Newman

    (Duke University
    Duke University)

  • Alexandra Schäfer

    (University of North Carolina at Chapel Hill)

  • Amanda Eaton

    (Duke University)

  • Justine Mae Flores

    (Duke University
    Duke University)

  • Austin Harner

    (Duke University
    Duke University)

  • Nicholas J. Catanzaro

    (University of North Carolina at Chapel Hill)

  • Michael L. Mallory

    (University of North Carolina at Chapel Hill)

  • Melissa D. Mattocks

    (University of North Carolina at Chapel Hill)

  • Christopher Beverly

    (Duke University
    Duke University)

  • Brianna Rhodes

    (Duke University
    Duke University)

  • Katayoun Mansouri

    (Duke University)

  • Elizabeth Itallie

    (Duke University
    Duke University)

  • Pranay Vure

    (Duke University
    Duke University)

  • Brooke Dunn

    (Duke University)

  • Taylor Keyes

    (Duke University)

  • Sherry Stanfield-Oakley

    (Duke University)

  • Christopher W. Woods

    (Duke University
    Duke University
    Duke University Medical Center)

  • Elizabeth A. Petzold

    (Duke University Medical Center)

  • Emmanuel B. Walter

    (Duke University
    Duke University)

  • Kevin Wiehe

    (Duke University
    Duke University)

  • Robert J. Edwards

    (Duke University
    Duke University)

  • David C. Montefiori

    (Duke University)

  • Guido Ferrari

    (Duke University
    Duke University
    Duke University
    Duke University)

  • Ralph Baric

    (University of North Carolina at Chapel Hill)

  • Derek W. Cain

    (Duke University
    Duke University)

  • Kevin O. Saunders

    (Duke University
    Duke University
    Duke University
    Duke University)

  • Barton F. Haynes

    (Duke University
    Duke University
    Duke University)

  • Mihai L. Azoitei

    (Duke University
    Duke University)

Abstract

Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.

Suggested Citation

  • A. Brenda Kapingidza & Daniel J. Marston & Caitlin Harris & Daniel Wrapp & Kaitlyn Winters & Dieter Mielke & Lu Xiaozhi & Qi Yin & Andrew Foulger & Rob Parks & Maggie Barr & Amanda Newman & Alexandra , 2023. "Engineered immunogens to elicit antibodies against conserved coronavirus epitopes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43638-9
    DOI: 10.1038/s41467-023-43638-9
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    References listed on IDEAS

    as
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