Authors
David R Martinez, Alexandra Schäfer, Sarah R Leist, Gabriela De la Cruz, Ande West, Elena N Atochina-Vasserman, Lisa C Lindesmith, Norbert Pardi, Robert Parks, Maggie Barr, Dapeng Li, Boyd Yount, Kevin O Saunders, Drew Weissman, Barton F Haynes, Stephanie A Montgomery, Ralph S Baric
Publication date
2021/8/27
Journal
Science
Volume
373
Issue
6558
Pages
991-998
Publisher
American Association for the Advancement of Science
Description
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 …
Total citations
20202021202220232024125754319
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