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

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, Rashida Moore, April Walker, Lijuan Yang, Shirin Munir, I-Ting Teng, Peter D. Kwong, Kennichi Dowdell, Hanh Nguyen, JungHyun Kim, Jeffrey I. Cohen, Reed F. Johnson, Nicole L. Garza, Laura E. Via, Daniel L. Barber, Ursula J. Buchholz () and Cyril Le Nouën ()
Additional contact information
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
Temeri Wilder-Kofie: National Institutes of Health
Rashida Moore: National Institutes of Health
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

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47784-6

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