tetano
Editor, Senior Moderator
Science
. 2021 Jun 22;eabi4506.
doi: 10.1126/science.abi4506. Online ahead of print.
Chimeric spike mRNA vaccines protect against Sarbecoviru s challenge in mice
David R Martinez[SUP] 1 [/SUP], Alexandra Schäfer[SUP] 2 [/SUP], Sarah R Leist[SUP] 2 [/SUP], Gabriela De la Cruz[SUP] 3 [/SUP], Ande West[SUP] 2 [/SUP], Elena N Atochina-Vasserman[SUP] 4 [/SUP], Lisa C Lindesmith[SUP] 2 [/SUP], Norbert Pardi[SUP] 4 [/SUP], Robert Parks[SUP] 5 [/SUP], Maggie Barr[SUP] 5 [/SUP], Dapeng Li[SUP] 5 [/SUP], Boyd Yount[SUP] 2 [/SUP], Kevin O Saunders[SUP] 5 [/SUP], Drew Weissman[SUP] 4 [/SUP], Barton F Haynes[SUP] 5 [/SUP], Stephanie A Montgomery[SUP] 6 [/SUP], Ralph S Baric[SUP] 1 [/SUP]
Affiliations
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 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.
. 2021 Jun 22;eabi4506.
doi: 10.1126/science.abi4506. Online ahead of print.
Chimeric spike mRNA vaccines protect against Sarbecoviru s challenge in mice
David R Martinez[SUP] 1 [/SUP], Alexandra Schäfer[SUP] 2 [/SUP], Sarah R Leist[SUP] 2 [/SUP], Gabriela De la Cruz[SUP] 3 [/SUP], Ande West[SUP] 2 [/SUP], Elena N Atochina-Vasserman[SUP] 4 [/SUP], Lisa C Lindesmith[SUP] 2 [/SUP], Norbert Pardi[SUP] 4 [/SUP], Robert Parks[SUP] 5 [/SUP], Maggie Barr[SUP] 5 [/SUP], Dapeng Li[SUP] 5 [/SUP], Boyd Yount[SUP] 2 [/SUP], Kevin O Saunders[SUP] 5 [/SUP], Drew Weissman[SUP] 4 [/SUP], Barton F Haynes[SUP] 5 [/SUP], Stephanie A Montgomery[SUP] 6 [/SUP], Ralph S Baric[SUP] 1 [/SUP]
Affiliations
- PMID: 34214046
- DOI: 10.1126/science.abi4506
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 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.