Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.

Publication Type
Journal Article
Year of Publication
Anderson, Evan J; Rouphael, Nadine G; Widge, Alicia T; Jackson, Lisa A; Roberts, Paul C; Makhene, Mamodikoe; Chappell, James D; Denison, Mark R; Stevens, Laura J; Pruijssers, Andrea J; McDermott, Adrian B; Flach, Britta; Lin, Bob C; Doria-Rose, Nicole A; O'Dell, Sijy; Schmidt, Stephen D; Corbett, Kizzmekia S; Swanson, Phillip A; Padilla, Marcelino; Neuzil, Kathy M; Bennett, Hamilton; Leav, Brett; Makowski, Mat; Albert, Jim; Cross, Kaitlyn; Edara, Venkata Viswanadh; Floyd, Katharine; Suthar, Mehul S; Martinez, David R; Baric, Ralph; Buchanan, Wendy; Luke, Catherine J; Phadke, Varun K; Rostad, Christina A; Ledgerwood, Julie E; Graham, Barney S; Beigel, John H; mRNA-1273 Study Group
N Engl J Med
Date Published
2020 Sep 29
CRID; mRNA-1273; Safety and Immunogenicity; SARS-CoV-2; Vaccine In Older Adults

BACKGROUND: Testing 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.

METHODS: We 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.

RESULTS: Solicited 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.

CONCLUSIONS: In 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 number, NCT04283461.).