• Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John McGettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, and COVE Study Group.
• From Brigham and Women's Hospital (L.R.B.), Boston, and Moderna, Cambridge (H.B., R.P., C.K., B.L., W.D., H.Z., S.H., M.I., J. Miller, T.Z.) - both in Massachusetts; Baylor College of Medicine (H.M.E.S.) and Centex Studies (J.S.) - both in Houston; Meridian Clinical Research, Savannah (B.E., S.K., A.B.), and Emory University (N.R.) and Atlanta Clinical Research Center (N.S.), Atlanta - all in Georgia; University of Maryland School of Medicine, Baltimore (K.K., K.N.), and National Institute of Allergy and Infectious Diseases, Bethesda (D.F., M.M., J. Mascola, L.P., J.L., B.S.G.) - both in Maryland; Saint Louis University School of Medicine, St. Louis (S.F.); University of Illinois, Chicago, Chicago (R.N.); George Washington University School of Medicine and Health Sciences, Washington, DC (D.D.); University of California, San Diego, San Diego (S.A.S.); Vanderbilt University School of Medicine, Nashville (C.B.C.); Quality of Life Medical and Research Center, Tucson, AZ (J. McGettigan); Johnson County Clin-Trials, Lenexa, KS (C.F.); Research Centers of America, Hollywood, FL (H.S.); and Fred Hutchinson Cancer Research Center, Seattle (L.C., P.G., H.J.).
• N. Engl. J. Med. 2021 Feb 4; 384 (5): 403416403-416.

BackgroundVaccines are needed to prevent coronavirus disease 2019 (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 stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.MethodsThis phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers 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 end point 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.ResultsThe 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.ConclusionsThe 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. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).Copyright © 2020 Massachusetts Medical Society.

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