Vaccination against Japanese encephalitis with IC51: systematic review on immunogenicity, duration of protection and safety

Abstract Japanese encephalitis is a disease caused by a flavivirus which is transmitted by mosquitos in endemic countries. Considering the potentially severe outcomes of the disease, vaccination is recommended for those at risk of exposure. During recent years, IC51 (IXIARO®, JESPECT®, JEVAL®) has increasingly been used to protect travellers from Europe and the USA. However, no systematic review exists that summarizes the currently available evidence on the immunogenicity and safety of this vaccine. We conducted a systematic review on the immunogenicity and safety of IC51, using the databases PubMed, MEDLINE, EMBASE and ClinicalTrials.gov (search date: 31 August 2019). Data extracted from included studies were grouped by outcomes and stratified by population and setting. Risk of bias (ROB) was assessed using the RoB 2 tool for randomized controlled trials (RCTs) and ROBINS-I for non-randomized studies. Due to high heterogeneity, meta-analysis was not performed. A total of 32 studies from 16 countries met the inclusion criteria (15 RCTs, 17 non-randomized studies). ROB was serious or high in the majority of studies. Seroprotection rates ranged from 93 to 100% in adults (seven studies) and from 91 to 100% in children (four studies). In the study involving adults aged 64 years and older, seroprotection was 65% with higher rates in persons who were previously vaccinated against tick-borne encephalitis virus. Safety was investigated in 27 studies. Rates of serious adverse events were below 5% in all age groups, with the majority not being causally related to the vaccine. IC51 is a safe vaccine with good seroprotective abilities in persons aged >2 months to <64 years. The body of evidence, however, is weakened by a large amount of heterogeneity in study and clinical trial methodology. Further well-designed RCTs with special risk groups are needed.