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Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults #MMPMID32991794
Anderson EJ; Rouphael NG; Widge AT; Jackson LA; Roberts PC; Makhene M; Chappell JD; Denison MR; Stevens LJ; Pruijssers AJ; McDermott AB; Flach B; Lin BC; Doria-Rose NA; O'Dell S; Schmidt SD; Corbett KS; Swanson PA 2nd; Padilla M; Neuzil KM; Bennett H; Leav B; Makowski M; Albert J; Cross K; Edara VV; Floyd K; Suthar MS; Martinez DR; Baric R; Buchanan W; Luke CJ; Phadke VK; Rostad CA; Ledgerwood JE; Graham BS; Beigel JH
N Engl J Med 2020[Dec]; 383 (25): 2427-2438 PMID32991794show ga
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 mug or 100 mug 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-mug 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-mug 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-mug dose induced higher binding- and neutralizing-antibody titers than the 25-mug dose, which supports the use of the 100-mug 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.).
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N+Engl+J+Med 2020 ; 383 (25): 2427-2438
