Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice

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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,...

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Detalles Bibliográficos
Autores principales: Martinez, David R., Schäfer, Alexandra, Leist, Sarah R., De la Cruz, Gabriela, West, Ande, Atochina-Vasserman, Elena N., Lindesmith, Lisa C., Pardi, Norbert, Parks, Robert, Barr, Maggie, Li, Dapeng, Yount, Boyd, Saunders, Kevin O., Weissman, Drew, Haynes, Barton F., Montgomery, Stephanie A., Baric, Ralph S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899822/
https://www.ncbi.nlm.nih.gov/pubmed/34214046
http://dx.doi.org/10.1126/science.abi4506
Descripción
Sumario: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.

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