Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.
2020 Sep 29
Journal Article
Authors:
Anderson, E.J.;
Rouphael, N.G.;
Widge, A.T.;
Jackson, L.A.;
Roberts, P.C.;
Makhene, M.;
Chappell, J.D.;
Denison, M.R.;
Stevens, L.J.;
Pruijssers, A.J.;
McDermott, A.B.;
Flach, B.;
Lin, B.C.;
Doria-Rose, N.A.;
O'Dell, S.;
Schmidt, S.D.;
Corbett, K.S.;
Swanson, P.A.;
Padilla, M.;
Neuzil, K.M.;
Bennett, H.;
Leav, B.;
Makowski, M.;
Albert, J.;
Cross, K.;
Edara, V.Viswanadh;
Floyd, K.;
Suthar, M.S.;
Martinez, D.R.;
Baric, R.;
Buchanan, W.;
Luke, C.J.;
Phadke, V.K.;
Rostad, C.A.;
Ledgerwood, J.E.;
Graham, B.S.;
Beigel, J.H.
Secondary:
N Engl J Med
PMID:
32991794
URL:
https://pubmed.ncbi.nlm.nih.gov/32991794/
Keywords:
CRID; mRNA-1273; Safety and Immunogenicity; SARS-CoV-2; Vaccine In Older Adults
Abstract:
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.).
