Five accelerated schedules for the tick-borne encephalitis vaccine FSME-Immun® in last-minute travellers: an open-label, single-centre, randomized controlled pilot trial

Abstract

Abstract Background The purpose of this exploratory study was to evaluate different accelerated tick-borne encephalitis (TBE) vaccine schedules for last-minute travellers. Methods In a single-centre, open-label pilot study, 77 TBE-naïve Belgian soldiers were randomized to one of the following five schedules with FSME-Immun®: group 1 (‘classical accelerated’ schedule) received one intramuscular (IM) dose at Day 0 and Day 14, group 2 two IM doses at Day 0, group 3 two intradermal (ID) doses at Day 0, group 4 two ID doses at Day 0 and Day 7 and group 5 two ID doses at Day 0 and Day 14. The last dose(s) of the primary vaccination scheme were given after 1 year: IM (1 dose) or ID (2 doses). TBE virus neutralizing antibodies were measured in a plaque reduction neutralization test (PRNT90 and 50) at Days 0, 14, 21, 28, Months 3, 6, 12 and 12+21 days. Seropositivity was defined as neutralizing antibody titres ≥10. Results The median age was 19–19.5 years in each group. Median time to seropositivity up to Day 28 was shortest for PRNT90 in ID-group 4 and for PRNT50 in all ID groups. Seroconversion until Day 28 peaked highest for PRNT90 in ID-group 4 (79%) and for PRNT50 in ID-groups 4 and 5 (both 100%). Seropositivity after the last vaccination after 12 months was high in all groups. Previous yellow fever vaccination was reported in 16% and associated with lower geometric mean titres of TBE-specific antibodies at all-time points. The vaccine was generally well tolerated. However, mild to moderate local reactions occurred in 73–100% of ID compared with 0–38% of IM vaccinations, and persistent discolouration was observed in nine ID vaccinated individuals. Conclusion The accelerated two-visit ID schedules might offer a better immunological alternative to the recommended classical accelerated IM schedule, but an aluminium-free vaccine would be preferable.