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

Kizzmekia S. Corbett , Darin K. Edwards , Sarah R. Leist , 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 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 , Kaichun 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 , Vladimir 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 Alvarado , Martha 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 Carfı́ , Barney S. Graham
2020 Nature 1,567 citations

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. mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.

Keywords

PreparednessSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)VirologyPathogen2019-20 coronavirus outbreakBiologyComputational biologyMedicineImmunologyOutbreakInfectious disease (medical specialty)DiseasePolitical scienceInternal medicine

MeSH Terms

2019-nCoV Vaccine mRNA-1273AnimalsAntibodiesNeutralizingBetacoronavirusCD8-Positive T-LymphocytesCOVID-19COVID-19 VaccinesClinical TrialsPhase III as TopicCoronavirus InfectionsFemaleLungMiceMutationNosePandemicsPneumoniaViralRNAMessengerRNAViralSARS-CoV-2Th1 CellsToll-Like Receptor 4Viral Vaccines

Affiliated Institutions

Related Publications

Publication Info

Year
2020
Type
article
Volume
586
Issue
7830
Pages
567-571
Citations
1567
Access
Closed

External Links

Download PDF (Free) View on DOI.org PubMed Semantic Scholar

Social Impact

Altmetric
PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

1567
OpenAlex
54
Influential

Cite This

Kizzmekia S. Corbett, Darin K. Edwards, Sarah R. Leist et al. (2020). SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature , 586 (7830) , 567-571. https://doi.org/10.1038/s41586-020-2622-0

Identifiers

DOI
10.1038/s41586-020-2622-0
PMID
32756549
PMCID
PMC7581537

Data Quality

Data completeness: 86%