Safety and immunogenicity of the modified adult tick-borne encephalitis vaccine FSME-IMMUN ®: Results of two large phase 3 clinical studies

A prospective, randomised, multicentre, single-blind phase 3 study was performed to assess the safety of a vaccination schedule consisting of two vaccinations (21–35 days apart) with the tick-borne encephalitis (TBE) vaccine FSME-IMMUN ® “adults” (five consecutive lots) in comparison to another licensed TBE vaccine (Encepur ®, with polygeline) (two lots) in healthy volunteers ( n = 3966) aged 16–65 years. The safety of the third vaccination with FSME-IMMUN ® “adults” (6 months after the first vaccination) was investigated in a follow-up study on the same population ( n = 3705) and TBE antibody titres were analysed pre- and post-vaccination in a subgroup of volunteers ( n = 564). Following the first vaccination, the overall incidence of fever (≥38.0 °C) was 0.8% in the FSME-IMMUN ® “adults” study group and 5.6% in the comparator study group; fever was mainly mild. The fever rate after the second vaccination was 0.6% and 0.5% in the two study groups, respectively. Local and systemic reactions after the first vaccination occurred with a lower frequency in the FSME-IMMUN ® “adults” study group than in the comparator group. Upon analysing the tolerability of the third vaccination with FSME-IMMUN ® “adults”, similar results were determined in both study groups of volunteers previously vaccinated with FSME-IMMUN ® “adults” or with the comparator vaccine. The immunogenicity results demonstrated similar seroconversion rates (as determined by ELISA or neutralization test) before and after the third vaccination in the FSME-IMMUN ® “adults” group and in the comparator group respectively. The results of both studies demonstrate that: (1) FSME-IMMUN ® “adults” is safe and highly immunogenic, (2) all five production lots of FSME-IMMUN ® “adults” were consistent with respect to a low rate of adverse events, (3) FSME-IMMUN ® “adults” induces considerably lower adverse reaction rates than the comparator vaccine after the first vaccination, and (4) two vaccinations with the comparator vaccine can be successfully followed by a third vaccination with FSME-IMMUN ® “adults”.