학술논문
An intranasal vaccine durably protects against SARS-CoV-2 variants in mice
Document Type
article
Author
Ahmed O. Hassan; Swathi Shrihari; Matthew J. Gorman; Baoling Ying; Dansu Yaun; Saravanan Raju; Rita E. Chen; Igor P. Dmitriev; Elena Kashentseva; Lucas J. Adams; Colin Mann; Meredith E. Davis-Gardner; Mehul S. Suthar; Pei-Yong Shi; Erica Ollmann Saphire; Daved H. Fremont; David T. Curiel; Galit Alter; Michael S. Diamond
Source
Cell Reports, Vol 36, Iss 4, Pp 109452- (2021)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.