Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice

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  • Martinez, David R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Schäfer, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Leist, Sarah R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • de la Cruz, Gabriela
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • West, Ande
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Atochina-Vasserman, Elena N.
    • Other Affiliation: University of Pennsylvania Perelman School of Medicine
  • Lindesmith, Lisa C.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Pardi, Norbert
    • Other Affiliation: University of Pennsylvania Perelman School of Medicine
  • Parks, Robert
    • Other Affiliation: Duke University School of Medicine
  • Barr, Maggie
    • Other Affiliation: Duke University School of Medicine
  • Li, Dapeng
    • Other Affiliation: Duke University School of Medicine
  • Yount, Boyd
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Saunders, Kevin O.
    • Other Affiliation: Duke University School of Medicine
  • Weissman, Drew
    • Other Affiliation: University of Pennsylvania Perelman School of Medicine
  • Haynes, Barton F.
    • Other Affiliation: Duke University School of Medicine
  • Montgomery, Stephanie A.
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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.
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  • Article
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  • In Copyright
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  • Science
Language
  • English
ISSN
  • 1095-9203
  • 0036-8075

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