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Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice

Authors :
Elena N. Atochina-Vasserman
Ande West
Sarah R. Leist
Lisa C. Lindesmith
Alexandra Schäfer
Dapeng Li
Robert Parks
Norbert Pardi
Boyd Yount
Maggie Barr
Kevin O. Saunders
Stephanie A. Montgomery
Drew Weissman
Ralph S. Baric
Gabriela De la Cruz
Barton F. Haynes
David R. Martinez
Source :
Science, bioRxiv, article-version (status) pre, article-version (number) 1
Publication Year :
2021
Publisher :
American Association for the Advancement of Science (AAAS), 2021.

Abstract

The emergence of SARS-CoV and SARS-CoV-2 in the 21st century highlights the need to develop universal vaccination strategies against the SARS-related Sarbecovirus subgenus. Using structure-guided chimeric spike designs and multiplexed immunizations, we demonstrate protection against SARS-CoV, SARS-CoV-2, and bat CoV (BtCoV) RsSHC014 challenge in highly vulnerable aged mice. Chimeric spike mRNAs containing N-terminal domain (NTD), and receptor binding domains (RBD) induced high levels of broadly protective neutralizing antibodies against three high-risk sarbecoviruses: SARS-CoV, RsSHC014, and WIV-1. In contrast, SARS-CoV-2 mRNA vaccination not only showed a 10 to >500-fold reduction in neutralizing titers against heterologous sarbecovirus strains, but SARS-CoV challenge in mice resulted in breakthrough infection including measurable lung pathology. Importantly, chimeric spike mRNA vaccines efficiently neutralized both the D614G and the South African B.1.351 variants of concern despite some reduction in neutralization activity. Thus, multiplexed-chimeric spikes may provide a novel strategy to prevent pandemic and SARS-like zoonotic coronavirus infections, while revealing the limited efficacy of SARS-CoV-2 spike vaccines against other sarbecoviruses.

Details

ISSN :
10959203 and 00368075
Volume :
373
Database :
OpenAIRE
Journal :
Science
Accession number :
edsair.doi.dedup.....ee6106d321b50b8144a9ffbc52f64981
Full Text :
https://doi.org/10.1126/science.abi4506