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Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants

Author

Listed:
  • James Logue

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine)

  • Robert M. Johnson

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine)

  • Nita Patel

    (Novavax, Inc)

  • Bin Zhou

    (Novavax, Inc)

  • Sonia Maciejewski

    (Novavax, Inc)

  • Bryant Foreman

    (Novavax, Inc)

  • Haixia Zhou

    (Novavax, Inc)

  • Alyse D. Portnoff

    (Novavax, Inc)

  • Jing-Hui Tian

    (Novavax, Inc)

  • Asma Rehman

    (Novavax, Inc)

  • Marisa E. McGrath

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine)

  • Robert E. Haupt

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine)

  • Stuart M. Weston

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine)

  • Lauren Baracco

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine)

  • Holly Hammond

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine
    Johns Hopkins University, School of Medicine)

  • Mimi Guebre-Xabier

    (Novavax, Inc)

  • Carly Dillen

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine)

  • M. Madhangi

    (Novavax, Inc)

  • Ann M. Greene

    (Novavax, Inc)

  • Michael J. Massare

    (Novavax, Inc)

  • Greg M. Glenn

    (Novavax, Inc)

  • Gale Smith

    (Novavax, Inc)

  • Matthew B. Frieman

    (The University of Maryland School of Medicine
    The University of Maryland School of Medicine)

Abstract

SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351, and Omicron/BA.1. Mice vaccinated with two doses of Novavax prototype NVX-CoV2373 (rS-WU1) or rS-Beta alone, in combination, or heterologous prime-boost, are protected from challenge. Virus titer is undetectable in lungs in all vaccinated mice, and Th1-skewed cellular responses are observed. We tested sera from a panel of variant spike protein vaccines and find broad neutralization and inhibition of spike:ACE2 binding from the rS-Beta and rS-Delta vaccines against a variety of variants including Omicron. This study demonstrates that rS-Beta vaccine alone or in combination with rS-WU1 induces antibody-and cell-mediated responses that are protective against challenge with SARS-CoV-2 variants and offers broader neutralizing capacity than a rS-WU1 prime/boost regimen alone. Together, these nonhuman primate and murine data suggest a Beta variant booster dose could elicit a broad immune response to fight new and future SARS-CoV-2 variants.

Suggested Citation

  • James Logue & Robert M. Johnson & Nita Patel & Bin Zhou & Sonia Maciejewski & Bryant Foreman & Haixia Zhou & Alyse D. Portnoff & Jing-Hui Tian & Asma Rehman & Marisa E. McGrath & Robert E. Haupt & Stu, 2023. "Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35606-6
    DOI: 10.1038/s41467-022-35606-6
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    References listed on IDEAS

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    1. Jingyun Yang & Wei Wang & Zimin Chen & Shuaiyao Lu & Fanli Yang & Zhenfei Bi & Linlin Bao & Fei Mo & Xue Li & Yong Huang & Weiqi Hong & Yun Yang & Yuan Zhao & Fei Ye & Sheng Lin & Wei Deng & Hua Chen , 2020. "A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity," Nature, Nature, vol. 586(7830), pages 572-577, October.
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