A systematic review and meta-analysis of the immunogenicity and safety of Chikungunya vaccine

Abstract Background Since July 2025, there have been outbreaks of chikungunya fever in some parts of China, which has drawn widespread social attention. Vaccination is the most economical and effective means of preventing and controlling infectious diseases. Currently, there are two chikungunya fever vaccines approved for marketing worldwide, and there is still a lack of systematic review and analysis of the immunogenicity and safety of this vaccine. Objective Compare the levels in immunogenicity and safety of Chikungunya (CHIKV) vaccine. Methods Computerized searches were conducted in PubMed, EMBASE, Web of Science (WOS), Scopus, Cochrane Library and Clinicaltrials.gov for randomized controlled trials on the implementation of CHIKV vaccines in human populations. The search period was from the establishment of the databases to August 2025. Two researchers independently screened the literature, extracted the data and assessed the risk of bias in the included studies. Data analysis was performed using RevMan 5.4.1 software. Results In terms of immunogenicity, the results showed that there was a statistically significant difference in seroreponse rate: RR =12.22 (95% CI : 9.05∼16.51, I 2 =89%, P <0.00001), as well as GMR: RR =13.88 (95% CI : 4.12∼46.79, I 2 =0%, P <0.00001). In the meta-analysis of safety indicators, there was a statistically significant differences in any adverse reactions: RR =1.30(95% CI : 1.18∼1.42, I 2 =45%, P <0.00001). The meta-analysis results of local adverse reactions showed that there was a statistically significant differences in any local adverse reactions: RR =1.61 (95% CI :1.42∼1.82, I 2 =67%, P < 0.00001), as well as injection site pain: RR =1.83 (95% CI : 1.46∼2.28, I 2 =38%, P < 0.00001). The results showed that there were statistically significant difference in systemic solicited adverse events: RR =1.54(95% CI :1.44∼1.66, I 2 =87%, P <0.00001), as well as their common manifestations(including headache, fatigue, myalgia, arthralgia, nausea, fever). Conclusion CHIKV vaccine has demonstrated well immunogenicity. However, further research is still needed on the adverse events following vaccination. Author Summary Chikungunya fever, as a neglected tropical disease, experienced a relatively severe outbreak in the Guangdong region of China in 2025. Vaccination, as the most effective vaccination method, currently only has two approved vaccines globally. This study systematically reviewed the published RCTs results of different technical routes of chikungunya fever vaccines that have been on the market and are still in clinical trials, to understand, analyze and master the various immunogenicity and safety data of chikungunya fever vaccines. Study found that vaccination with the chikungunya fever vaccine was able to induce strong neutralizing antibodies and demonstrated an excellent seroreponse rate. However, in terms of safety, some significant adverse reactions were observed, especially in the overall adverse reaction rates such as headache, fatigue, muscle pain, fever, etc., as well as the local adverse reaction rates such as pain at the injection site. This inspires us to pay more attention to the safety of chikungunya fever vaccines in the future vaccine research and development process.