SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness

TLDR

A SARS‑CoV‑2 vaccine is needed to control the global COVID‑19 public health crisis. Atomic‑level structural insights guided prefusion‑stabilizing mutations that enhanced spike protein expression and immunogenicity, enabling rapid mRNA‑1273 vaccine production upon SARS‑CoV‑2 sequence release. mRNA‑1273 elicits strong neutralizing antibodies and CD8 T‑cell responses, protects mice from SARS‑CoV‑2 infection in lungs and noses without immunopathology, and is advancing from Phase 2 toward Phase 3 efficacy trials.

Abstract

Summary A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.