SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

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  • Corbett, K.S.
    • Other Affiliation: National Institutes of Health
  • Edwards, D.K.
    • Other Affiliation: Moderna Inc
  • Leist, S.R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Abiona, O.M.
    • Other Affiliation: National Institutes of Health
  • Boyoglu-Barnum, S.
    • Other Affiliation: National Institutes of Health
  • Gillespie, R.A.
    • Other Affiliation: National Institutes of Health
  • Himansu, S.
    • Other Affiliation: Moderna Inc
  • Schäfer, A.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Ziwawo, C.T.
    • Other Affiliation: National Institutes of Health
  • DiPiazza, A.T.
    • Other Affiliation: National Institutes of Health
  • Dinnon, K.H.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Elbashir, S.M.
    • Other Affiliation: Moderna Inc
  • Shaw, C.A.
    • Other Affiliation: Moderna Inc
  • Woods, A.
    • Other Affiliation: Moderna Inc
  • Fritch, E.J.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Martinez, D.R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Bock, K.W.
    • Other Affiliation: National Institutes of Health
  • Minai, M.
    • Other Affiliation: National Institutes of Health
  • Nagata, B.M.
    • Other Affiliation: National Institutes of Health
  • Hutchinson, G.B.
    • Other Affiliation: National Institutes of Health
  • Wu, K.
    • Other Affiliation: Moderna Inc
  • Henry, C.
    • Other Affiliation: Moderna Inc
  • Bahl, K.
    • Other Affiliation: Moderna Inc
  • Garcia-Dominguez, D.
    • Other Affiliation: Moderna Inc
  • Ma, L.Z.
    • Other Affiliation: Moderna Inc
  • Renzi, I.
    • Other Affiliation: Moderna Inc
  • Kong, W.-P.
    • Other Affiliation: National Institutes of Health
  • Schmidt, S.D.
    • Other Affiliation: National Institutes of Health
  • Wang, L.
    • Other Affiliation: National Institutes of Health
  • Zhang, Y.
    • Other Affiliation: National Institutes of Health
  • Phung, E.
    • Other Affiliation: National Institutes of Health
  • Chang, L.A.
    • Other Affiliation: National Institutes of Health
  • Loomis, R.J.
    • Other Affiliation: National Institutes of Health
  • Altaras, N.E.
    • Other Affiliation: Moderna Inc
  • Narayanan, E.
    • Other Affiliation: Moderna Inc
  • Metkar, M.
    • Other Affiliation: Moderna Inc
  • Presnyak, V.
    • Other Affiliation: Moderna Inc
  • Liu, C.
    • Other Affiliation: National Institutes of Health
  • Louder, M.K.
    • Other Affiliation: National Institutes of Health
  • Shi, W.
    • Other Affiliation: National Institutes of Health
  • Leung, K.
    • Other Affiliation: National Institutes of Health
  • Yang, E.S.
    • Other Affiliation: National Institutes of Health
  • West, A.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Gully, K.L.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Stevens, L.J.
    • Other Affiliation: Vanderbilt University Medical Center
  • Wang, N.
    • Other Affiliation: University of Texas at Austin
  • Wrapp, D.
    • Other Affiliation: University of Texas at Austin
  • Doria-Rose, N.A.
    • Other Affiliation: National Institutes of Health
  • Stewart-Jones, G.
    • Other Affiliation: Moderna Inc
  • Bennett, H.
    • Other Affiliation: Moderna Inc
  • Alvarado, G.S.
    • Other Affiliation: National Institutes of Health
  • Nason, M.C.
    • Other Affiliation: National Institutes of Health
  • Ruckwardt, T.J.
    • Other Affiliation: National Institutes of Health
  • McLellan, J.S.
    • Other Affiliation: University of Texas at Austin
  • Denison, M.R.
    • Other Affiliation: Vanderbilt University Medical Center
  • Chappell, J.D.
    • Other Affiliation: Vanderbilt University Medical Center
  • Moore, I.N.
    • Other Affiliation: National Institutes of Health
  • Morabito, K.M.
    • Other Affiliation: National Institutes of Health
  • Mascola, J.R.
    • Other Affiliation: National Institutes of Health
  • Baric, R.S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Carfi, A.
    • Other Affiliation: Moderna Inc
  • Graham, B.S.
    • Other Affiliation: National Institutes of Health
Abstract
  • A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy.
Date of publication
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DOI
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  • Article
Rights statement
  • In Copyright
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  • Public Domain 1.0
Journal title
  • Nature
Journal volume
  • 586
Journal issue
  • 7830
Page start
  • 567
Page end
  • 571
ISSN
  • 1476-4687

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