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

Kizzmekia S. Corbett, Darin K. Edwards, Sarah R. Leist, Olubukola M. Abiona, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, Sunny Himansu, Alexandra Schäfer, Cynthia T. Ziwawo, Anthony T. DiPiazza, Kenneth H. Dinnon, Sayda M. Elbashir, Christine A. Shaw, Angela Woods, Ethan J. Fritch, David R. Martinez, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Geoffrey B. Hutchinson, Kai Wu, Carole Henry, Kapil Bahl, Dario Garcia-Dominguez, LingZhi Ma, Isabella Renzi, Wing-Pui Kong, Stephen D. Schmidt, Lingshu Wang, Yi Zhang, Emily Phung, Lauren A. Chang, Rebecca J. Loomis, Nedim Emil Altaras, Elisabeth Narayanan, Mihir Metkar, Vlad Presnyak, Cuiping Liu, Mark K. Louder, Wei Shi, Kwanyee Leung, Eun Sung Yang, Ande West, Kendra L. Gully, Laura J. Stevens, Nianshuang Wang, Daniel Wrapp, Nicole A. Doria-Rose, Guillaume Stewart-Jones, Hamilton Bennett, Gabriela S. Alvarado, Martha C. Nason, Tracy J. Ruckwardt, Jason S. McLellan, Mark R. Denison, James D. Chappell, Ian N. Moore, Kaitlyn M. Morabito, John R. Mascola, Ralph S. Baric, Andrea Carfi () and Barney S. Graham ()
Additional contact information
Kizzmekia S. Corbett: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Darin K. Edwards: Moderna Inc
Sarah R. Leist: University of North Carolina at Chapel Hill
Olubukola M. Abiona: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Seyhan Boyoglu-Barnum: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Rebecca A. Gillespie: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Sunny Himansu: Moderna Inc
Alexandra Schäfer: University of North Carolina at Chapel Hill
Cynthia T. Ziwawo: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Anthony T. DiPiazza: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Kenneth H. Dinnon: University of North Carolina at Chapel Hill
Sayda M. Elbashir: Moderna Inc
Christine A. Shaw: Moderna Inc
Angela Woods: Moderna Inc
Ethan J. Fritch: University of North Carolina at Chapel Hill
David R. Martinez: University of North Carolina at Chapel Hill
Kevin W. Bock: National Institutes of Health
Mahnaz Minai: National Institutes of Health
Bianca M. Nagata: National Institutes of Health
Geoffrey B. Hutchinson: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Kai Wu: Moderna Inc
Carole Henry: Moderna Inc
Kapil Bahl: Moderna Inc
Dario Garcia-Dominguez: Moderna Inc
LingZhi Ma: Moderna Inc
Isabella Renzi: Moderna Inc
Wing-Pui Kong: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Stephen D. Schmidt: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Lingshu Wang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Yi Zhang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Emily Phung: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Lauren A. Chang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Rebecca J. Loomis: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Nedim Emil Altaras: Moderna Inc
Elisabeth Narayanan: Moderna Inc
Mihir Metkar: Moderna Inc
Vlad Presnyak: Moderna Inc
Cuiping Liu: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Mark K. Louder: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Wei Shi: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Kwanyee Leung: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Eun Sung Yang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Ande West: University of North Carolina at Chapel Hill
Kendra L. Gully: University of North Carolina at Chapel Hill
Laura J. Stevens: Vanderbilt University Medical Center
Nianshuang Wang: University of Texas at Austin
Daniel Wrapp: University of Texas at Austin
Nicole A. Doria-Rose: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Guillaume Stewart-Jones: Moderna Inc
Hamilton Bennett: Moderna Inc
Gabriela S. Alvarado: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Martha C. Nason: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Tracy J. Ruckwardt: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Jason S. McLellan: University of Texas at Austin
Mark R. Denison: Vanderbilt University Medical Center
James D. Chappell: Vanderbilt University Medical Center
Ian N. Moore: National Institutes of Health
Kaitlyn M. Morabito: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
John R. Mascola: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Ralph S. Baric: University of North Carolina at Chapel Hill
Andrea Carfi: Moderna Inc
Barney S. Graham: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Nature, 2020, vol. 586, issue 7830, 567-571

Abstract: 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: 2020
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DOI: 10.1038/s41586-020-2622-0

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