A phase 1, randomized, placebo-controlled, dose-ranging study to evaluate the safety and immunogenicity of an mRNA-based chikungunya virus vaccine in healthy adults

Background: Chikungunya, a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), causes a significant global health burden, and there is currently no approved vaccine to prevent chikun-gunya disease. In this study, the safety and immunogenicity of a CHIKV mRNA vaccine candidate (mRNA-1388) were evaluated in healthy participants in a CHIKV-nonendemic region.Methods: This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study enrolled healthy adults (ages 18-49 years) between July 2017 and March 2019 in the United States. Participants were randomly assigned (3:1) to receive 2 intramuscular injections 28 days apart with mRNA-1388 in 3 dose-level groups (25 & mu;g, 50 & mu;g, and 100 & mu;g) or placebo and were followed for up to 1 year. Safety (unsolicited adverse events [AEs]), tolerability (local and systemic reactogenicity; solicited AEs), and immunogenicity (geometric mean titers [GMTs] of CHIKV neutralizing and binding antibodies) of mRNA-1388 versus placebo were evaluated.Results: Sixty participants were randomized and received > 1 vaccination; 54 (90%) completed the study. mRNA-1388 demonstrated favorable safety and reactogenicity profiles at all dose levels. Immunization with mRNA-1388 induced substantial and persistent humoral responses. Dose-dependent increases in neutralizing antibody titers were observed; GMTs (95% confidence intervals [CIs]) at 28 days after dose 2 were 6.2 (5.1-7.6) for mRNA-1388 25 & mu;g, 53.8 (26.8-108.1) for mRNA-1388 50 & mu;g, 92.8 (43.6-197.6) for mRNA-1388 100 & mu;g, and 5.0 (not estimable) for placebo. Persistent humoral responses were observed up to 1 year after vaccination and remained higher than placebo in the 2 higher mRNA-1388 dose groups. The development of CHIKV-binding antibodies followed a similar trend as that observed with neutraliz-ing antibodies.Conclusions: mRNA-1388, the first mRNA vaccine against CHIKV, was well tolerated and elicited substan-tial and long-lasting neutralizing antibody responses in healthy adult participants in a nonendemic region.ClinicalTrials.gov: NCT03325075.& COPY; 2023 Published by Elsevier Ltd.