Interim data show mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in trial participants
The mRNA-1273 vaccine induced anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses in all participants, and no trial-limiting safety concerns were identified, according to interim data published in The New England Journal of Medicine.
The first participant received the candidate vaccine on March 16, 2020. The current interim report details the initial findings from the first 45 participants, aged 18 to 55 years, enrolled at Kaiser Permanente Washington Health Research Institute in Seattle, Washington, and at the Emory University School of Medicine in Atlanta, Georgia.
Three groups of 15 participants received 2 intramuscular injections, 28 days apart, of either 25, 100 or 250 μg of the investigational vaccine. All the participants received 1 injection; 42 received both scheduled injections. Three participants did not receive the second vaccination, including one in the 25-μg group who had urticaria on both legs, with onset 5 days after the first vaccination, and two (one each in the 25-μg and 250-μg groups) who missed the second vaccination window owing to isolation for suspected COVID-19 while test results, ultimately negative, were pending.
“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),” reported Lisa A. Jackson, MD, Kaiser Permanente Washington Health Research Institute, Seattle, Washington, and colleagues.
The authors added that after the second vaccination, serum-neutralising activity was detected by 2 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.
Further, the authors noted no serious adverse events. After the first vaccination, solicited systemic adverse events were reported by 5 participants (33%) in the 25-μg group, 10 (67%) in the 100-μg group, and 8 (53%) in the 250-μg group, with all being mild or moderate in severity. However, solicited systemic adverse events were more common after the second vaccination and occurred in seven of 13 participants in the 25-μg group, all 15 subjects in the 100-μg group, and all 14 of those in the 250-μg group, with 3 of those participants (21%) reporting one or more severe events. Across both vaccinations, solicited systemic and local adverse events that occurred in more than half the participants included fatigue, chills, headache and myalgia, as well as pain at the injection site.
“These safety and immunogenicity findings support advancement of the mRNA-1273 vaccine to later-stage clinical trials,” the authors wrote. They noted that of the three doses evaluated, the 100-μg dose “elicits high neutralization responses and Th1-skewed CD4 T cell responses, coupled with a reactogenicity profile that is more favorable than that of the higher dose.”
The authors said a phase 2 trial of mRNA-1273 in 600 healthy adults, evaluating doses of 50 μg and 100 μg, is ongoing, while a large phase 3 efficacy trial, evaluating the 100-μg dose, is anticipated to begin later.