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bioRxiv · 10.1101/2021.03.11.434872

Chimeric spike mRNA vaccines protect against sarbecovirus challenge in mice

Martinez, D. R.·Schaefer, A.·Leist, S. R.·De la Cruz, G.·West, A.·Atochina-Vasserman, E. N.·Parks, R.·Barr, M.·Li, D.·Yount, B.·Saunders, K. O.·Weissman, D.·Haynes, B.·Montgomery, S. A.·Baric, R. S.
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Abstract

The emergence of 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 mRNAs induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. In 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 infection. Chimeric spike mRNA vaccines efficiently neutralized D614G, UK B.1.1.7., mink cluster five, and the South African B.1.351 variant of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential. SentenceChimerized RBD, NTD, and S2 spike mRNA-LNPs protect mice against epidemic, zoonotic, and pandemic SARS-like viruses

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Martinez, D. R., Schaefer, A., Leist, S. R., De la Cruz, G., West, A., Atochina-Vasserman, E. N., Parks, R., Barr, M., Li, D., Yount, B., Saunders, K. O., Weissman, D., Haynes, B., Montgomery, S. A., Baric, R. S.. 2021-03-12. Chimeric spike mRNA vaccines protect against sarbecovirus challenge in mice. https://doi.org/10.1101/2021.03.11.434872

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