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Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques

Author

Listed:
  • Jaclyn A. Kaiser

    (National Institutes of Health)

  • Christine E. Nelson

    (National Institutes of Health)

  • Xueqiao Liu

    (National Institutes of Health)

  • Hong-Su Park

    (National Institutes of Health)

  • Yumiko Matsuoka

    (National Institutes of Health)

  • Cindy Luongo

    (National Institutes of Health)

  • Celia Santos

    (National Institutes of Health)

  • Laura R. H. Ahlers

    (National Institutes of Health)

  • Richard Herbert

    (National Institutes of Health)

  • Ian N. Moore

    (National Institutes of Health
    Emory University)

  • Temeri Wilder-Kofie

    (National Institutes of Health
    National Institutes of Health)

  • Rashida Moore

    (National Institutes of Health
    Emory University)

  • April Walker

    (National Institutes of Health)

  • Lijuan Yang

    (National Institutes of Health)

  • Shirin Munir

    (National Institutes of Health)

  • I-Ting Teng

    (National Institutes of Health)

  • Peter D. Kwong

    (National Institutes of Health)

  • Kennichi Dowdell

    (National Institutes of Health)

  • Hanh Nguyen

    (National Institutes of Health)

  • JungHyun Kim

    (National Institutes of Health)

  • Jeffrey I. Cohen

    (National Institutes of Health)

  • Reed F. Johnson

    (National Institutes of Health)

  • Nicole L. Garza

    (National Institutes of Health)

  • Laura E. Via

    (National Institutes of Health)

  • Daniel L. Barber

    (National Institutes of Health)

  • Ursula J. Buchholz

    (National Institutes of Health)

  • Cyril Le Nouën

    (National Institutes of Health)

Abstract

Immunization via the respiratory route is predicted to increase the effectiveness of a SARS-CoV-2 vaccine. Here, we evaluate the immunogenicity and protective efficacy of one or two doses of a live-attenuated murine pneumonia virus vector expressing SARS-CoV-2 prefusion-stabilized spike protein (MPV/S-2P), delivered intranasally/intratracheally to male rhesus macaques. A single dose of MPV/S-2P is highly immunogenic, and a second dose increases the magnitude and breadth of the mucosal and systemic anti-S antibody responses and increases levels of dimeric anti-S IgA in the airways. MPV/S-2P also induces S-specific CD4+ and CD8+ T-cells in the airways that differentiate into large populations of tissue-resident memory cells within a month after the boost. One dose induces substantial protection against SARS-CoV-2 challenge, and two doses of MPV/S-2P are fully protective against SARS-CoV-2 challenge virus replication in the airways. A prime/boost immunization with a mucosally-administered live-attenuated MPV vector could thus be highly effective in preventing SARS-CoV-2 infection and replication.

Suggested Citation

  • Jaclyn A. Kaiser & Christine E. Nelson & Xueqiao Liu & Hong-Su Park & Yumiko Matsuoka & Cindy Luongo & Celia Santos & Laura R. H. Ahlers & Richard Herbert & Ian N. Moore & Temeri Wilder-Kofie & Rashid, 2024. "Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47784-6
    DOI: 10.1038/s41467-024-47784-6
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