Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice.
Journal Article (Journal Article)
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable aged mice. Chimeric spike messenger RNAs (mRNAs) induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. By contrast, SARS-CoV-2 mRNA vaccination not only showed a marked reduction in neutralizing titers against heterologous Sarbecoviruses, but SARS-CoV and WIV-1 challenge in mice resulted in breakthrough infections. Chimeric spike mRNA vaccines efficiently neutralized D614G, mink cluster five, and the UK B.1.1.7 and South African B.1.351 variants of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential.
- Martinez, DR; Schäfer, A; Leist, SR; De la Cruz, G; West, A; Atochina-Vasserman, EN; Lindesmith, LC; Pardi, N; Parks, R; Barr, M; Li, D; Yount, B; Saunders, KO; Weissman, D; Haynes, BF; Montgomery, SA; Baric, RS
- August 27, 2021
Volume / Issue
- 373 / 6558
Start / End Page
- 991 - 998
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States