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

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Apr 26;15(1):3553.
doi: 10.1038/s41467-024-47784-6. Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques

Jaclyn A Kaiser[SUP] 1 [/SUP], Christine E Nelson[SUP] #[/SUP][SUP] 2 [/SUP], Xueqiao Liu[SUP] #[/SUP][SUP] 1 [/SUP], Hong-Su Park[SUP] 1 [/SUP], Yumiko Matsuoka[SUP] 1 [/SUP], Cindy Luongo[SUP] 1 [/SUP], Celia Santos[SUP] 1 [/SUP], Laura R H Ahlers[SUP] 1 [/SUP], Richard Herbert[SUP] 3 [/SUP], Ian N Moore[SUP] 4 5 [/SUP], Temeri Wilder-Kofie[SUP] 4 6 [/SUP], Rashida Moore[SUP] 4 7 [/SUP], April Walker[SUP] 8 [/SUP], Lijuan Yang[SUP] 1 [/SUP], Shirin Munir[SUP] 1 [/SUP], I-Ting Teng[SUP] 9 [/SUP], Peter D Kwong[SUP] 9 [/SUP], Kennichi Dowdell[SUP] 10 [/SUP], Hanh Nguyen[SUP] 10 [/SUP], JungHyun Kim[SUP] 10 [/SUP], Jeffrey I Cohen[SUP] 10 [/SUP], Reed F Johnson[SUP] 11 [/SUP], Nicole L Garza[SUP] 11 [/SUP], Laura E Via[SUP] 8 [/SUP], Daniel L Barber[SUP] 2 [/SUP], Ursula J Buchholz[SUP] 12 [/SUP], Cyril Le Nouën[SUP] 13 [/SUP]



Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.


 
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