1. Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques.
- Author
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Kaiser JA, Nelson CE, Liu X, Park HS, Matsuoka Y, Luongo C, Santos C, Ahlers LRH, Herbert R, Moore IN, Wilder-Kofie T, Moore R, Walker A, Yang L, Munir S, Teng IT, Kwong PD, Dowdell K, Nguyen H, Kim J, Cohen JI, Johnson RF, Garza NL, Via LE, Barber DL, Buchholz UJ, and Le Nouën C
- Subjects
- Animals, Male, Mice, CD8-Positive T-Lymphocytes immunology, Genetic Vectors immunology, Genetic Vectors genetics, Antibodies, Neutralizing immunology, Administration, Intranasal, Vaccines, Attenuated immunology, Vaccines, Attenuated administration & dosage, Immunoglobulin A immunology, CD4-Positive T-Lymphocytes immunology, Humans, Macaca mulatta, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology, Spike Glycoprotein, Coronavirus genetics, COVID-19 prevention & control, COVID-19 immunology, COVID-19 virology, Immunization, Secondary, Antibodies, Viral immunology
- 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., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)- Published
- 2024
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