Background
There is an urgent need for fair and equitable access to safe and effective vaccines to end the COVID-19 pandemic. Shortages in reagents and vaccines are a major challenge, as well as limited knowledge on dose response relationship with mRNA COVID-19 vaccines. We explored intradermal fractional dose administration of a mRNA SARS-CoV-2/COVID-19 vaccine as a potential dose-sparing strategy.
Methods
We conducted a proof-of-concept, dose-escalation, open-label, randomised-controlled vaccine trial (IDSCOVA) in healthy adults aged 18-30 years. To test initial safety, ten participants received 10 μg mRNA-1273 vaccine through intradermal injection at day 1 and 29. Following a favourable safety review, thirty participants were 1:1 randomised to receive 20 μg mRNA-1273 either intradermally or intramuscularly. The primary endpoint was tolerability and safety. The secondary endpoint was seroconversion and specific IgG concentration against SARS-CoV-2 spike S1 and Receptor Binding Domain (RBD) after the second dose at day 43. We compared results to two historical cohorts of non-hospitalised COVID-19 patients and vaccinated individuals.
Findings
Thirty-eight of forty included participants (median age 25 years) completed the study. There were no serious adverse events. Self-reported local adverse reactions after intradermal delivery were mild, both in the 10 μg and the 20 μg group. In the higher dose group, systemic adverse reactions were more common, but still well tolerated. All 38 participants mounted substantially higher IgG-anti-S1 and IgG-anti-RBD concentrations at day 43 than COVID-19 controls. At day 43, anti-S1 (95% CI) was 1,696 (1,309-2,198) BAU/mL for the 10 μg intradermal group, 1,406 (953.5-2,074) BAU/mL for the 20 μg intramuscular group and 2,057 (1,421-2,975) BAU/mL for the 20 μg intradermal group. Anti-S1 was 107.2 (63-182.2) BAU/mL for the convalescent plasma control group and 1,558 (547.8-4,433) BAU/mL for the individuals vaccinated with 100 μg mRNA-1273.
Interpretation
Intradermal administration of 10 μg and 20 μg mRNA-1273 vaccine was well tolerated and safe, and resulted in a robust antibody response. Intradermal vaccination has the potential to be deployed for vaccine dose-sparing.
Tolerability, Safety and Immunogenicity of Intradermal Delivery of a Fractional Dose mRNA -1273 SARS-CoV-2 Vaccine in Healthy Adults as a Dose Sparing Strategy
