The authors conducted a phase 1, dose-escalation, open-label clinical trial designed to determine the safety, reactogenicity and immunogenicity of an mRNA vaccine against SARS-CoV-2.
Study design
The study involved 45 healthy adults, 18 to 55 years of age, who received 2 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. The trial was conducted at 2 centers in the United States and the vaccine was administered as a 0.5-mL injection in the deltoid muscle on days 1 and 29; follow-up visits were scheduled for 7 and 14 days after each vaccination and on days 57, 119, 209, and 394.
Outcomes
After the first vaccination, antibody responses were highest with high-dose group. After the second vaccination, the titers increased in all groups and serum-neutralizing activity was detected by 2 methods in all participants, 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 high dose.
Limitations
Participants were not screened for SARS-CoV-2 infection by serology or polymerase chain reaction before enrollment and the study patients were a limited population in a single country with a narrow age range of young and healthy volunteers. In addition, participants were followed only through day 57, so the authors were not able to assess the durability of the immune responses. The very young and elderly were not evaluated. Further studies are required to assess the vaccine in various population groups including children and older age groups, those with comorbidities and individuals from geographically diverse populations over a longer time frame.
Clinical significance
The mRNA-1273 vaccine induced anti–COVID-19 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. This study is entering phase 3 of clinical trials in the United States with an anticipated enrollment of 30,000 volunteers.
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