Abstract Background Chikungunya virus is a re-emerging global threat. Two vaccines—one live-attenuated and one virus-like particle (VLP)—have received approval. However, comparative safety and immunogenicity data across platforms and special populations remain limited. Methods We conducted a living systematic review (LSR) and meta-analysis of clinical and preclinical studies evaluating the safety and immunogenicity of chikungunya vaccines. Databases were searched biweekly (2014–2025). Outcomes included adverse events, pregnancy outcomes, and immunogenicity (seroprotection, seroconversion), stratified by age group, vaccine platform (live-attenuated, VLP, mRNA, vector), and baseline serostatus. Meta-analyses used random-effects models; absolute and relative risks were calculated with 95% confidence intervals (CI). Results We included 55 studies (18 clinical, 37 preclinical). Trials enrolled 8,279 vaccinated participants: 7,560 adults and 719 adolescents. Two studies reported 16 post-vaccination pregnancies, with five spontaneous abortions—three assessed as unrelated and two reported as unrelated serious adverse events in independent safety review. In seronegative adults, live-attenuated vaccines were associated with increased risk of arthralgia (RR 2.95, 95% CI 2.29–3.79), fever (RR 11.01, 95% CI 6.37–19.03), and headache (RR 2.07, 95% CI 1.78–2.40); similar trends were observed in adolescents. Seroprotection outcomes were reported as incremental proportions (IP) comparing vaccinated and placebo groups. In adolescents, IPs were 0.94 (95% CI 0.87–1.01) with VLA1553 and 0.68 (95% CI 0.59–0.76) with PXVX0317 at 30 days, increasing to 0.95 (95% CI 0.90–1.00) at 365 days. In adults, VLA1553 reached 0.99 (95% CI 0.97–1.01) at 30 days; PXVX0317 reached 0.86 (95% CI 0.81–0.91) at 30 days and 0.74 (95% CI 0.68–0.81) at 365 days; mRNA-1388 maintained 1.00 (95% CI 0.76–1.24) throughout. Seroconversion mirrored seroprotection. Conclusion Chikungunya vaccines show high immunogenicity across platforms. Live-attenuated vaccines are more reactogenic in seronegative individuals. Data on pregnancy remains limited. Our LSR supports continued evidence synthesis and post-licensure safety monitoring. Disclosures Flor M. Munoz, MD, Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
Sambade et al. (Thu,) studied this question.