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.

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

  • 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
  • mRNA-1273 vaccine