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; Barney S Graham

doi:10.1038/s41586-020-2622-0

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

Nature. 2020 Oct;586(7830):567-571. doi: 10.1038/s41586-020-2622-0. Epub 2020 Aug 5.

Authors

Kizzmekia S Corbett^#¹, Darin K Edwards^#², Sarah R Leist^#³, Olubukola M Abiona¹, Seyhan Boyoglu-Barnum¹, Rebecca A Gillespie¹, Sunny Himansu², Alexandra Schäfer³, Cynthia T Ziwawo¹, Anthony T DiPiazza¹, Kenneth H Dinnon³, Sayda M Elbashir², Christine A Shaw², Angela Woods², Ethan J Fritch⁴, David R Martinez³, Kevin W Bock⁵, Mahnaz Minai⁵, Bianca M Nagata⁵, Geoffrey B Hutchinson¹, Kai Wu², Carole Henry², Kapil Bahl², Dario Garcia-Dominguez², LingZhi Ma², Isabella Renzi², Wing-Pui Kong¹, Stephen D Schmidt¹, Lingshu Wang¹, Yi Zhang¹, Emily Phung^{1

6}, Lauren A Chang¹, Rebecca J Loomis¹, Nedim Emil Altaras², Elisabeth Narayanan², Mihir Metkar², Vlad Presnyak², Cuiping Liu¹, Mark K Louder¹, Wei Shi¹, Kwanyee Leung¹, Eun Sung Yang¹, Ande West³, Kendra L Gully³, Laura J Stevens⁷, Nianshuang Wang⁸, Daniel Wrapp⁸, Nicole A Doria-Rose¹, Guillaume Stewart-Jones², Hamilton Bennett², Gabriela S Alvarado¹, Martha C Nason⁹, Tracy J Ruckwardt¹, Jason S McLellan⁸, Mark R Denison⁷, James D Chappell⁷, Ian N Moore⁵, Kaitlyn M Morabito¹, John R Mascola¹, Ralph S Baric^{3

4}, Andrea Carfi¹⁰, Barney S Graham¹¹

Affiliations

¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
² Moderna Inc, Cambridge, MA, USA.
³ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁶ Institute for Biomedical Sciences, George Washington University, Washington, DC, USA.
⁷ Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
⁹ Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁰ Moderna Inc, Cambridge, MA, USA. [email protected].
¹¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

2019-nCoV Vaccine mRNA-1273
Animals
Antibodies, Neutralizing / immunology
Betacoronavirus / genetics
Betacoronavirus / immunology*
CD8-Positive T-Lymphocytes / immunology
COVID-19
COVID-19 Vaccines
Clinical Trials, Phase III as Topic
Coronavirus Infections / genetics
Coronavirus Infections / immunology*
Coronavirus Infections / prevention & control*
Coronavirus Infections / virology
Female
Lung / immunology
Lung / virology
Mice
Mutation
Nose / immunology
Nose / virology
Pandemics / prevention & control*
Pneumonia, Viral / immunology*
Pneumonia, Viral / prevention & control*
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
Viral Vaccines / immunology*

Substances

Antibodies, Neutralizing
COVID-19 Vaccines
RNA, Messenger
RNA, Viral
Tlr4 protein, mouse
Toll-Like Receptor 4
Viral Vaccines
2019-nCoV Vaccine mRNA-1273

Abstract

Publication types

MeSH terms

Substances

Grants and funding