Safety and immunogenicity of a mRNA-based chikungunya vaccine in a phase 1 dose-ranging trial

Purpose: Despite the public health impact and threat of Chikungunya virus, a globally re-emerging mosquito-borne alphavirus, there are currently no effective therapeutic or preventative options available. This phase 1 study investigates the safety and immunogenicity of a mRNA-based chikungunya vaccine. Methods & Materials: We are conducting a phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study to evaluate the safety and immunogenicity of mRNA-1388 (VAL-181388), a mRNA-based vaccine for chikungunya, in healthy adults aged 18–49 years in a non-endemic region in the United States. Subjects are assigned to one of three dose level cohorts, 25 μg, 50 μg or 100 μg, each randomized 3:1 active to placebo. Intramuscular injections are administered on weeks 0 and 4, and subjects are followed for 1 year after the last injection. The primary endpoint is to assess safety of the vaccine. The secondary endpoint is to assess immunogenicity by measuring chikungunya-specific neutralizing and binding antibody titers. Results: A total of 60 participants were assigned to receive 25 μg (n = 15), 50 μg (n = 15), or 100 μg (n = 15) of mRNA-1388, or placebo (n = 15). The study is fully enrolled and an interim analysis of safety and immunogenicity has been conducted on data through 1 month after the second vaccination. The vaccine was well-tolerated at all dose levels. Immunogenicity was assessed on the primary Intent-to-Treat dataset. A dose-dependent increase in neutralizing and binding antibody titers was observed, with a substantial boost after the second vaccination, and an associated 100% seroconversion for all subjects administered 100 μg of mRNA-1388. Conclusion: The mRNA-based chikungunya vaccine is safe, well-tolerated, and immunogenic, and therefore a promising vaccine candidate worthy of further development.