Dubischar Katrin L, Kadlecek Vera, Sablan Jr Benjamin, Borja-Tabora Charissa Fay, Gatchalian Salvacion, Eder-Lingelbach Susanne, Kiermayr Sigrid, Spruth Martin, Westritschnig Kerstin
From the *Valneva Austria Gmbh, Vienna, Austria; †Department of Pediatrics, University of the Philippines, ‡Department of Health, Research Institute for Tropical Medicine, and §Section of Infectious and Tropical Diseases, Department of Pediatrics, University of the Philippines, College of Medicine, Philippine General Hospital, Manila, Philippines; and ¶Department of Health, Research Institute for Tropical Medicine, Muntinlupa, Philippines.
Pediatr Infect Dis J. 2017 Sep;36(9):898-904. doi: 10.1097/INF.0000000000001615.
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.
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.
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.
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.
日本脑炎(乙脑)是亚洲主要的公共卫生问题,对包括儿童在内的非流行国家的旅行者构成虽小但潜在致命的威胁。欧洲和美国尚无用于儿科的乙脑疫苗。
年龄分层的2个月至17岁儿童队列接受2剂Vero细胞衍生的灭活乙脑病毒疫苗(IXIARO;奥地利维也纳的Valneva Austria GmbH公司),间隔28天给药[<3岁,0.25 mL(成人剂量的一半);≥3岁,0.5 mL(成人全剂量)]。免疫原性终点为血清转化率、乙脑中和抗体滴度4倍增长以及几何平均滴度,在496名意向性治疗人群的受试者首次接种疫苗后56天和7个月进行评估。还根据接种前乙脑病毒和登革病毒血清状态分析了两个时间点对乙脑病毒的免疫反应。
在第56天,≥99.2%的受试者按年龄适当剂量给药后实现血清转化,各年龄组中77.4% - 100%报告滴度有4倍增长,几何平均滴度在176至687之间,年龄较小的儿童免疫反应最强。在第7个月,85.5% - 100%的受试者维持血清转化。既往乙脑病毒免疫在第56天不影响免疫反应;然而,它导致在第7个月保护性抗体滴度的更好持续性。
在儿科人群中测试的两种剂量下,IXIARO均具有高度免疫原性,在接受适当年龄剂量的>99%的受试者中第56天产生保护性抗体滴度。