SARS-CoV-2 Vaccine Candidate Yields Promising Findings in Phase 1 Trial
An mRNA vaccine candidate against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) yielded promising phase 1 trial findings, which were published in the New England Journal of Medicine.
The vaccine (mRNA-1273) was codeveloped by researchers from the National Institute of Allergy and Infectious Diseases and Moderna.
“The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified,” the authors of the trial concluded. “These findings support further development of this vaccine,” they added.
The authors arrived at their conclusion after performing a phase 1, dose-escalation, open-label trial of 45 healthy adult participants aged 18 to 55 years. Participants were administered 2 vaccinations with mRNA-1273 in a dose of 25 μg (n = 15), 100 μg (n = 15), or 250 μg (n = 15), with 28 days between each dose.
The results of the study indicated that antibody responses increased with higher doses of the vaccine following administration of the first dose of the vaccine. At day 29, enzyme- linked immunosorbent assay anti–S-2P antibody geometric mean titer (GMT) was 40,227 for 25 μg, 109,209 for 100 μg, and 213,526 for 250 μg. The titers increased after the second dose of the vaccine, with GMTs at day 57 of 299,751for 25 μg, 782,719 for 100 μg, and 1,192,154 μg for 250 μg.
The researchers noted the detection of serum-neutralizing activity via 2 methods among all participants in the present analysis. Values were found to be “generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens,” they wrote.
One participant in the 25-μg group was withdrawn after the first vaccination due to an unsolicited adverse event (transient urticaria). Fatigue, headache, chills, injection site pain, and myalgia were among the solicited adverse events that were recorded in more than half of participants in the trial. Systemic adverse events were found to be more common after the second dose was administered, especially in the highest dose group. One or more severe adverse events were reported among 3 (21%) participants who received the 250-μg dose. Fever was reported in 6 (40%) of the participants in the 100-μg group and 8 (57%) participants in the 250-μg group, with one event (maximum temperature 39.6°C) considered to be severe.
Two doses of the mRNA-1273 vaccine (50 μg and 100 μg) are currently being tested in a phase 2 trial of 600 healthy adults, the researchers wrote, adding that a large phase 3 efficacy trial of a 100-μg dose is expected to begin this summer.
Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS-CoV-2 — preliminary report. N Eng J Med. Published online July 14, 2020. doi:10.1056/NEJMoa2022483