Nature communications · 2024
Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Kaiser Jaclyn A, Nelson Christine E, Liu Xueqiao, Park Hong-Su, Matsuoka Yumiko, Luongo Cindy, Santos Celia, Ahlers Laura R H, Herbert Richard, Moore Ian N, Wilder-Kofie Temeri, Moore Rashida, Walker April, Yang Lijuan, Munir Shirin, Teng I-Ting, Kwong Peter D, Dowdell Kennichi, Nguyen Hanh, Kim JungHyun, Cohen Jeffrey I, Johnson Reed F, Garza Nicole L, Via Laura E, Barber Daniel L, Buchholz Ursula J, Le Nouën Cyril
Аннотация
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.