Vaccination against chikungunya - a systematic review on the immunogenicity, tolerability, and safety of the live-attenuated vaccine (LAV) Ixchiq and the virus like particle (VLP) vaccine Vimkunya

BACKGROUND: Infections with the chikungunya virus are increasingly reported due to many reasons including climate change. Two vaccines against chikungunya have recently been approved in Europe, the live-attenuated vaccine (LAV) Ixchiq and the virus like particle (VLP) vaccine Vimkunya. However, no systematic review of phase 3 clinical trial data has been published that summarizes the currently available evidence on the immunogenicity, tolerability, and safety of these vaccines. Therefore, these data were systematically analyzed by a working group of the German Standing Committee on Vaccination (STIKO) and the German Society for Tropical Medicine, Travel Medicine and Global Health (DTG). METHODS: We conducted a systematic review of the immunogenicity, tolerability and safety of Ixchiq and Vimkunya using Embase and PubMed (OVID) according to predefined PICO criteria, including placebo-controlled randomized control trials, cohort, and case-control studies. Risk of bias (RoB) was assessed with the RoB 2-tool. Additionally, post-marketing safety data were studied. RESULTS: Clinical efficacy data were not available. Instead, seropositivity rates above a predefined threshold served as a surrogate of protection. Both vaccines demonstrated strong immunogenicity with seroprotection rates for Ixchiq of >98% after 4 weeks, and for Vimkunya after 3 weeks of >97% in 12-59-year-olds and > 87% in ≥65-year-olds. In the pivotal studies, both vaccines showed also an acceptable safety profile. Post-marketing safety data showed a higher risk for serious adverse events in elderly patients for Ixchiq. CONCLUSION: In addition to mosquito protection and vector control, two vaccines with a good efficacy profile based on the surrogate marker of seroprotection are now available to prevent chikungunya. While both vaccines showed acceptable tolerability, the safety of vaccines must be continuously assessed based on further data from post-marketing surveillance of the respective populations.