Intradermal (ID) delivery of fractional doses of mRNA-1273 vaccine was safe and immunogenic in a proof-of-concept study. If confirmed in larger trials, this dose-sparing technique could be used to immunize more people with a limited vaccine stockpile, the authors note.
In April and May 2021, participants aged 18 to 30 years were recruited in the Netherlands for this dose-escalation, open-label, randomized controlled trial of the mRNA-1273 COVID-19 vaccine. In part 1 of the study, 10 participants received one-tenth of the standard dose of mRNA-1273 (10 mcg) by ID injection on days 1 and 29. In part 2 of the trial, 30 participants were randomized to ID and intramuscular (IM) 20-mcg doses on days 1 and 29.
All participants showed a robust antibody response at day 43 that persisted to 7 months. “The binding antibody responses for anti-S1 IgG, anti-[receptor-binding domain] IgG, and neutralizing antibodies showed similar patterns,” the researchers report. “At day 43, geometric mean concentrations of neutralizing antibody were 1115 IU/mL (95% CI, 669 to 1858 IU/mL) for the 10-mcg group, 1300 IU/mL (CI, 941 to 1796 IU/mL) for the 20-mcg ID group, and 1052 IU/mL (CI, 733 to 1509 IU/mL) for the 20-mcg IM group. The IgA responses were similar between groups, independent of dose or method of administration.”
These antibody concentrations are within ranges correlated with high levels of protection in the phase 3 trial of mRNA-1273, particularly for the 20-mcg dose. The authors conclude that “the safety and immunogenicity results from this trial strongly support advancement of the investigation of ID vaccination with the mRNA-1273 vaccine.”