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

Nature
Kizzmekia S CorbettBarney S Graham

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.

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Datasets Mentioned

BETA
AFS88936
MN908947.3

Methods Mentioned

BETA
dissect
enzyme-linked immunosorbent assay
ELISA
nanoprecipitation
transfection
fluorescence-activated cell sorting
FACS
density gradient centrifugation

Software Mentioned

Prism
GraphPad
FlowJo
R

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