mRNA-1273 Vaccine Phase 1 Trial Demonstrates Robust Antibody and Neutralisation Response Against SARS-CoV-2
This dose-escalation phase 1 trial of the mRNA-1273 COVID-19 vaccine in 45 healthy adults showed dose-dependent anti-spike antibody responses after two vaccinations, with neutralising activity comparable to convalescent sera at all dose levels. Solicited systemic adverse events were more common after the second dose, particularly at 250 ug. The immunogenicity data, measured by ELISA and neutralisation assays, supported rapid advancement to phase 3 and established serological biomarker thresholds for vaccine development.
The original study
An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.
- Authors
- Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al.
- Journal
- The New England journal of medicine
- Type
- Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- PMID
- 32663912
Original abstract
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. METHODS: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group. RESULTS: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events. CONCLUSIONS: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).