Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice

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.

Source: Science: Current Issue - August 26, 2021 Category: Science Authors: Martinez, D. R., Schäfer, A., Leist, S. R., De la Cruz, G., West, A., Atochina-Vasserman, E. N., Lindesmith, L. C., Pardi, N., Parks, R., Barr, M., Li, D., Yount, B., Saunders, K. O., Weissman, D., Haynes, B. F., Montgomery, S. A., Baric, R. S. Tags: Immunology, Microbiology r-articles Source Type: research