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

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.

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 ClinicalTrials.gov number, NCT04283461.)