Vaccines are needed to prevent COVID-19 and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilised full-length spike protein of the SARS-CoV-2. This phase 3 randomised, observer-blinded, placebo-controlled trial was conducted at 99 centres across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary endpoint was prevention of COVID-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic COVID-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe COVID-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.
The authors concluded that the mRNA-1273 vaccine showed 94.1% efficacy at preventing COVID-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified.