Comparison of immunogenicity and safety of licensed Japanese encephalitis vaccines: A systematic review and network meta-analysis

Introduction: Annually more than 100,000 Japanese encephalitis (JE) cases and 25,000 deaths worldwide are caused by JE virus infection. More than 15 JE vaccines are currently in use worldwide. It is unknown whether any of the vaccines is superior to the others in terms of immunogenicity and safety. Methods: Four databases were systematically searched for randomised controlled trials that compared two or more types of JE vaccines. Vaccines were classified into four classes: inactivated mouse brain-derived (oldest class), inactivated Vero cell, live chimeric, and live attenuated. Network meta-analysis was used to generate mixed effect estimates against inactivated mouse brain-derived vaccines for seroconversion, and against placebo for adverse event (AE) and severe adverse event (SAE). Results: 23 studies (38,496 participants) were included. All newer vaccine classes had better immunogenicity, the difference was statistically significant for inactivated Vero cell (OR = 2.98; 95 %CI: 1.02–8.65) and live chimeric (OR = 5.93; 95 %CI: 1.73–20.32) vaccines. Inactivated mouse-derived vaccines had the highest odds for AEs (OR = 2.27; 95 %CI: 1.59–3.23), the odds of AE of newer vaccines was not different to placebo. There was no difference in SAEs across vaccine classes. Conclusions: All newer JE vaccines have comparable safety profiles, live chimeric and inactivated Vero cell vaccines are the most immunogenic among the newer vaccine classes.