• Evan J Anderson, Nadine G Rouphael, Alicia T Widge, Lisa A Jackson, Paul C Roberts, Mamodikoe Makhene, James D Chappell, Mark R Denison, Laura J Stevens, Andrea J Pruijssers, Adrian B McDermott, Britta Flach, Bob C Lin, Nicole A Doria-Rose, Sijy O'Dell, Stephen D Schmidt, Kizzmekia S Corbett, Phillip A Swanson, Marcelino Padilla, Kathy M Neuzil, Hamilton Bennett, Brett Leav, Mat Makowski, Jim Albert, Kaitlyn Cross, Venkata Viswanadh Edara, Katharine Floyd, Mehul S Suthar, David R Martinez, Ralph Baric, Wendy Buchanan, Catherine J Luke, Varun K Phadke, Christina A Rostad, Julie E Ledgerwood, Barney S Graham, John H Beigel, and mRNA-1273 Study Group.
• From the Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta and the Department of Pediatrics, Emory University School of Medicine (E.J.A., V.V.E., K.F., M.S.S., C.A.R.), and Emory Vaccine Center, Yerkes National Primate Research Center, Emory University (M.S.S.), Atlanta, and Hope Clinic, Department of Medicine, Emory University School of Medicine, Decatur (E.J.A., N.G.R., V.K.P.) - both in Georgia; the Vaccine Research Center (A.T.W., A.B.M., B.F., B.C.L., N.A.D.-R., S.O., S.D.S., K.S.C., P.A.S., M.P., J.E.L., B.S.G.) and the Division of Microbiology and Infectious Diseases (P.C.R., M. Makhene, W.B., C.J.L., J.H.B.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, the University of Maryland School of Medicine, Baltimore (K.M.N.), and the Emmes Company, Rockville (M. Makowski, J.A., K.C.) - all in Maryland; Kaiser Permanente Washington Health Research Institute, Seattle (L.A.J.); the Department of Pediatrics (J.D.C., M.R.D., L.J.S., A.J.P.), the Vanderbilt Institute for Infection, Immunology, and Inflammation (J.D.C., M.R.D., A.J.P.), and the Departments of Pathology, Microbiology, and Immunology (M.R.D.), Vanderbilt University Medical Center, Nashville; Moderna, Cambridge, MA (H.B., B.L.); and the Departments of Epidemiology and Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill (D.R.M., R.B.).
• N. Engl. J. Med. 2020 Dec 17; 383 (25): 2427-2438.

BackgroundTesting of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age.MethodsWe conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart.ResultsSolicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti-S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells.ConclusionsIn this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.).Copyright © 2020 Massachusetts Medical Society.

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