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


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.

SUBMITTER: Corbett KS 

PROVIDER: S-EPMC7581537 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Corbett Kizzmekia S KS   Edwards Darin K DK   Leist Sarah R SR   Abiona Olubukola M OM   Boyoglu-Barnum Seyhan S   Gillespie Rebecca A RA   Himansu Sunny S   Schäfer Alexandra A   Ziwawo Cynthia T CT   DiPiazza Anthony T AT   Dinnon Kenneth H KH   Elbashir Sayda M SM   Shaw Christine A CA   Woods Angela A   Fritch Ethan J EJ   Martinez David R DR   Bock Kevin W KW   Minai Mahnaz M   Nagata Bianca M BM   Hutchinson Geoffrey B GB   Wu Kai K   Henry Carole C   Bahl Kapil K   Garcia-Dominguez Dario D   Ma LingZhi L   Renzi Isabella I   Kong Wing-Pui WP   Schmidt Stephen D SD   Wang Lingshu L   Zhang Yi Y   Phung Emily E   Chang Lauren A LA   Loomis Rebecca J RJ   Altaras Nedim Emil NE   Narayanan Elisabeth E   Metkar Mihir M   Presnyak Vlad V   Liu Cuiping C   Louder Mark K MK   Shi Wei W   Leung Kwanyee K   Yang Eun Sung ES   West Ande A   Gully Kendra L KL   Stevens Laura J LJ   Wang Nianshuang N   Wrapp Daniel D   Doria-Rose Nicole A NA   Stewart-Jones Guillaume G   Bennett Hamilton H   Alvarado Gabriela S GS   Nason Martha C MC   Ruckwardt Tracy J TJ   McLellan Jason S JS   Denison Mark R MR   Chappell James D JD   Moore Ian N IN   Morabito Kaitlyn M KM   Mascola John R JR   Baric Ralph S RS   Carfi Andrea A   Graham Barney S BS  

Nature 20200805 7830


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<sup>1</sup>. 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 co  ...[more]

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