COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge

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  • DiPiazza, A.T.
    • Other Affiliation: National Institutes of Health
  • Leist, S.R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Abiona, O.M.
    • Other Affiliation: National Institutes of Health
  • Moliva, J.I.
    • Other Affiliation: National Institutes of Health
  • Werner, A.
    • Other Affiliation: National Institutes of Health
  • Minai, M.
    • Other Affiliation: National Institutes of Health
  • Nagata, B.M.
    • Other Affiliation: National Institutes of Health
  • Bock, K.W.
    • Other Affiliation: National Institutes of Health
  • Phung, E.
    • Other Affiliation: National Institutes of Health
  • Schäfer, A.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Dinnon, K.H., III
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Chang, L.A.
    • Other Affiliation: National Institutes of Health
  • Loomis, R.J.
    • Other Affiliation: National Institutes of Health
  • Boyoglu-Barnum, S.
    • Other Affiliation: National Institutes of Health
  • Alvarado, G.S.
    • Other Affiliation: National Institutes of Health
  • Sullivan, N.J.
    • Other Affiliation: National Institutes of Health
  • Edwards, D.K.
    • Other Affiliation: Moderna, Inc.
  • Morabito, K.M.
    • Other Affiliation: National Institutes of Health
  • Mascola, J.R.
    • Other Affiliation: National Institutes of Health
  • Carfi, A.
    • Other Affiliation: Moderna, Inc.
  • Corbett, K.S.
    • Other Affiliation: National Institutes of Health
  • Moore, I.N.
    • Other Affiliation: National Institutes of Health
  • Baric, R.S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Graham, B.S.
    • Other Affiliation: National Institutes of Health
  • Ruckwardt, T.J.
    • Other Affiliation: National Institutes of Health
Abstract
  • Vaccine-associated enhanced respiratory disease (VAERD) was previously observed in some preclinical models of SARS and MERS coronavirus vaccines. We used the SARS-CoV-2 MA10 mouse model of acute lung injury to evaluate the immune response and potential for immunopathology in animals vaccinated with research-grade mRNA-1273. Whole-inactivated virus or heat-denatured spike protein subunit vaccines with alum designed to elicit low-potency antibodies and Th2-skewed CD4+ T cells resulted in reduced viral titers and weight loss postchallenge, but more severe pathological changes in the lung compared to saline-immunized animals. In contrast, a protective dose of mRNA-1273 induced favorable humoral and cellular immune responses that protected from viral replication in the upper and lower respiratory tract upon challenge. A subprotective dose of mRNA-1273 reduced viral replication and limited histopathological manifestations compared to animals given saline. Overall, our findings demonstrate an immunological signature associated with antiviral protection without disease enhancement following vaccination with mRNA-1273.
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  • Article
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  • In Copyright
Journal title
  • Immunity
Language
  • English
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  • Postprint
ISSN
  • 1074-7613
Publisher
  • Cell Press

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