Yonekawa M, et al. Phase 3 immunogenicity and safety study of a tick-borne encephalitis vaccine in healthy Japanese participants 1 year of age and older. Vaccine. 2024;42(13):3180-3189. doi:10.1016/j.vaccine.2024.03.071
Although TBE virus has been reported in Japan since 1993, no TBE vaccine has been developed to date. In the frame of a licensure procedure, a phase 3 multicenter, single-arm, open label clinical study has been conducted in healthy Japanese participants at least 1 year of age and less than 16 years of age (pediatric, group 1, N=65) and in participants aged at least 16 years (adults, group 2) to assess safety and immunogenicity. Pediatric or adult vaccine formulations (TBE-EU strain Neudörfl, FSME Immun) were applied on day 1, visit 2 (21 to 35 days later) and visit 4 (150 to 365 days after dose 2), respectively. Blood samples for immunogenicity assessments were collected at visits 3 and 5 (4 weeks after dose 2 and 3; NT testing and two different ELISAs based on European virus strains).
A total of 98.0% of the adult and pediatric participants achieved neutralization seropositivity (NT titer 1:10) four weeks after the third dose: (95 % CI: 92.9 %, 99.8 %) and 100.0 % (95 % CI: 94.5 %, 100.0 %), respectively. Both age groups met the protocol-defined NT seropositivity rate threshold of >90% for the evaluable immunogenicity population based on the lower bound of the 95 % CI.
The percentages of adult and pediatric participants achieving TBE virus neutralization seropositivity 4 weeks after dose 2 were 93.0 % (95 % CI: 86.1 %, 97.1 %) and 92.3 % (95 % CI, 83.0 %, 97.5 %), respectively, slightly lower than those achieving NT seropositivity after dose 3.
Both adult and pediatric participants achieved the primary immunogenicity objective four weeks after receiving dose 3. As shown in this study, neither Japanese encephalitis vaccination nor previous infection had an apparent effect on the percentage of participants who achieved TBEV neutralization seropositivity.
There were similar frequencies of local reactions in both adult and pediatric groups, and all of them were mild to moderate in severity. The most frequently reported local reaction within 7 days of receiving a vaccination dose was pain at the injection site, which was reported by 36.4 % to 50.0 % of adults and 26.2 % to 43.1 % of children. The median duration of local reactions was 1 to 2 days in both groups apart from redness and swelling (3 days each) after dose 2 in the pediatric group.
Most systemic events were mild or moderate in severity. A median duration of 1 to 2.5 days was reported for systemic events in both groups apart from fevers in the adult group after dose 1 (6.5 days, n = 2) and after dose 2 (5 days, n = 1).
To conclude, this was a phase 3 study designed to support the Japanese government’s approval of a TBE vaccine based on the European Neudörfl strain. It assessed the vaccine’s immunogenicity and safety among healthy Japanese subjects ≥1 years of age. In Japanese adult and pediatric participants, TBE vaccine was safe and well tolerated, with results consistent with those reported in non-Japanese populations.