Nature Communications (Apr 2024)
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,
- Cyril Le Nouën
Affiliations
- Jaclyn A. Kaiser
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Christine E. Nelson
- T-Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Xueqiao Liu
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Hong-Su Park
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Yumiko Matsuoka
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Cindy Luongo
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Celia Santos
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Laura R. H. Ahlers
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Richard Herbert
- Experimental Primate Virology Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Ian N. Moore
- Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Temeri Wilder-Kofie
- Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Rashida Moore
- Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- April Walker
- Tuberculosis Imaging Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Lijuan Yang
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Shirin Munir
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- I-Ting Teng
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Peter D. Kwong
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Kennichi Dowdell
- Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Hanh Nguyen
- Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- JungHyun Kim
- Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Jeffrey I. Cohen
- Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Reed F. Johnson
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Nicole L. Garza
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Laura E. Via
- Tuberculosis Imaging Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Daniel L. Barber
- T-Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Ursula J. Buchholz
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Cyril Le Nouën
- RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- DOI
- https://doi.org/10.1038/s41467-024-47784-6
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
