BACKGROUND:Japanese encephalitis (JE) is a major public health concern in Asia and poses a small but potentially fatal threat to travelers from nonendemic countries, including children. No JE vaccine for pediatric use has been available in Europe and the United States. METHODS:Age-stratified cohorts of children between 2 months and 17 years received2 doses of Vero cell-derived inactivated JE virus vaccine (IXIARO; Valneva Austria GmbH, Vienna, Austria) administered 28 days apart [<3 years, 0.25 mL (half adult dose); ≥3 years, 0.5 mL (full adult dose)]. Immunogenicity endpoints were seroconversion rate, 4-fold increase in JEneutralizing antibody titer and geometric mean titer assessed 56 days and 7 months after the first vaccination in 496 subjects of the intent-to-treat population. The immune response to JE virus at both time points was also analyzed according to prevaccination JE virus and dengue virus serostatus. RESULTS: At day 56, seroconversion was attained in ≥99.2% of subjects with age-appropriate dosing, 4-fold increases in titer were reported for 77.4%-100% in various age groups, and geometric mean titers ranged from 176 to 687, with younger children having the strongest immune response. At month 7, seroconversion was maintained in 85.5%-100% of subjects. Pre-existing JE virus immunity did not impact on immune response at day 56; however, it led to a better persistence of protective antibody titers at month 7. CONCLUSIONS: IXIARO is highly immunogenic at both doses tested in the pediatric population, leading to protective antibody titers at day 56 in >99% of subjects who received the age-appropriate dose.
RCT Entities:
BACKGROUND:Japanese encephalitis (JE) is a major public health concern in Asia and poses a small but potentially fatal threat to travelers from nonendemic countries, including children. No JE vaccine for pediatric use has been available in Europe and the United States. METHODS: Age-stratified cohorts of children between 2 months and 17 years received 2 doses of Vero cell-derived inactivated JE virus vaccine (IXIARO; Valneva Austria GmbH, Vienna, Austria) administered 28 days apart [<3 years, 0.25 mL (half adult dose); ≥3 years, 0.5 mL (full adult dose)]. Immunogenicity endpoints were seroconversion rate, 4-fold increase in JE neutralizing antibody titer and geometric mean titer assessed 56 days and 7 months after the first vaccination in 496 subjects of the intent-to-treat population. The immune response to JE virus at both time points was also analyzed according to prevaccination JE virus and dengue virus serostatus. RESULTS: At day 56, seroconversion was attained in ≥99.2% of subjects with age-appropriate dosing, 4-fold increases in titer were reported for 77.4%-100% in various age groups, and geometric mean titers ranged from 176 to 687, with younger children having the strongest immune response. At month 7, seroconversion was maintained in 85.5%-100% of subjects. Pre-existing JE virus immunity did not impact on immune response at day 56; however, it led to a better persistence of protective antibody titers at month 7. CONCLUSIONS: IXIARO is highly immunogenic at both doses tested in the pediatric population, leading to protective antibody titers at day 56 in >99% of subjects who received the age-appropriate dose.