The Safety and Efficacy of the Chikungunya Virus Vaccine: A Systematic Review and Meta Analysis.

Background: Chikungunya virus (CHIKV) infection has an impact on global health, which emphasize the need for effective and safe vaccines. Several clinical trials have evaluated different vaccine platforms, including live-attenuated and virus-like particle (VLP) vaccines. The aim of this study is assessed the immunogenicity and safety of CHIKV vaccines across available clinical trials. Methods: A systematic review and meta-analysis of 11 clinical trials including 12,871 participants was conducted. Four vaccines were evaluated: live-attenuated candidates (VLA1553, TSI-GSD-218) and VLP vaccines (PXVX0317, VRC-CHKVLP059-00-VP). Trials included participants from endemic and non-endemic regions and were predominantly randomized, double-blind, and placebo-controlled. Seroresponse outcomes were examined at 15 days, 1 month, and 6 months. Risk of bias was assessed, and sensitivity analyses were performed to assess heterogeneity. Results: Vaccine recipients showed consistently higher seroresponse rates at all follow-up points. Live attenuated vaccines demonstrated statistically significant and robust immunogenicity at 15 days, 1 month, and 6 months. VLP vaccines generated favorable but non-significant pooled effects, with heterogeneity influenced by individual trials. Safety analyses revealed higher adverse event rates in vaccine groups compared with placebo, primarily driven by live-attenuated vaccines; however, events were mostly mild to moderate. VLP vaccines showed a safety profile similar to placebo. Conclusion: CHIKV vaccine candidates, particularly live-attenuated platforms, demonstrate strong immunogenicity with acceptable safety profiles. VLP vaccines appear safe with moderate immunogenicity. Further long term follow-up and additional large-scale trials are needed to support global vaccine implementation.