학술논문
Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques
Document Type
article
Author
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
Source
Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024)
Subject
Language
English
ISSN
2041-1723
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.