1. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness.
- Author
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Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, Himansu S, Schäfer A, Ziwawo CT, DiPiazza AT, Dinnon KH, Elbashir SM, Shaw CA, Woods A, Fritch EJ, Martinez DR, Bock KW, Minai M, Nagata BM, Hutchinson GB, Wu K, Henry C, Bahl K, Garcia-Dominguez D, Ma L, Renzi I, Kong WP, Schmidt SD, Wang L, Zhang Y, Phung E, Chang LA, Loomis RJ, Altaras NE, Narayanan E, Metkar M, Presnyak V, Liu C, Louder MK, Shi W, Leung K, Yang ES, West A, Gully KL, Stevens LJ, Wang N, Wrapp D, Doria-Rose NA, Stewart-Jones G, Bennett H, Alvarado GS, Nason MC, Ruckwardt TJ, McLellan JS, Denison MR, Chappell JD, Moore IN, Morabito KM, Mascola JR, Baric RS, Carfi A, and Graham BS
- Subjects
- 2019-nCoV Vaccine mRNA-1273, Animals, Antibodies, Neutralizing immunology, Betacoronavirus genetics, CD8-Positive T-Lymphocytes immunology, COVID-19, COVID-19 Vaccines, Clinical Trials, Phase III as Topic, Coronavirus Infections genetics, Coronavirus Infections virology, Female, Lung immunology, Lung virology, Mice, Mutation, Nose immunology, Nose virology, Pneumonia, Viral virology, RNA, Messenger genetics, RNA, Viral genetics, SARS-CoV-2, Th1 Cells immunology, Toll-Like Receptor 4 agonists, Toll-Like Receptor 4 immunology, Viral Vaccines chemistry, Viral Vaccines genetics, Betacoronavirus immunology, Coronavirus Infections immunology, Coronavirus Infections prevention & control, Pandemics prevention & control, Pneumonia, Viral immunology, Pneumonia, Viral prevention & control, Viral Vaccines immunology
- 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 immunogenicity
1 . 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.- Published
- 2020
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