Wijesinghe Pushpa Ranjan, Abeysinghe M R Nihal, Yoksan Sutee, Yao Yafu, Zhou Benli, Zhang Lei, Fleming Jessica A, Marfin Anthony A, Victor John C
Epidemiological Unit, Ministry of Healthcare and Nutrition, Colombo, Sri Lanka.
Mahidol University, Bangkok, Thailand.
Vaccine. 2016 Nov 21;34(48):5923-5928. doi: 10.1016/j.vaccine.2016.10.028. Epub 2016 Oct 20.
The performance of live attenuated Japanese Encephalitis SA 14-14-2 vaccine (CD-JEV) among children previously given inactivated mouse brain-derived JE vaccine (IMBV) is unknown. We evaluated the safety and immunogenicity of CD-JEV administered to 2- and 5-year-old children in Sri Lanka.
In this open-label, single arm trial in the Colombo District of Sri Lanka, generally healthy children 2 and 5years of age who had previously received two and three doses of IMBV, respectively, were administered one dose of CD-JEV subcutaneously. Participants were monitored for adverse events for one year post-vaccination. Serum neutralizing antibody responses were evaluated pre and 28 and 365days post-vaccination using JE plaque reduction neutralization test and characterized as the proportion of participants seroconverting. Seroconversion was defined as either reaching a titer considered seroprotective (⩾1:10) among participants with a baseline titer <1:10 or achieving at least a 4-fold rise in titer among participants with a baseline titer ⩾1:10.
Of 305 children given CD-JEV, 294 were included in the primary analysis of immunogenicity. Prior to vaccination, 144/147 (98.0%) 2-year-olds and 146/147 (99.3%) 5-year-olds had seroprotective levels. 28days post-vaccination, 79/147 [53.7% (95% CI, 45.3-62.0)] 2-year olds and of 60/147 [40.8% (95% CI, 32.8-49.2)] 5-year olds achieved seroconversion. Among 2-year-olds, geometric mean titers (GMTs) rose from 697 to 3175 28days post-vaccination. Among 5-year-olds, GMTs rose from 926 to 2776. Most adverse reactions were mild, and no serious adverse events were related to study vaccination.
Administration of CD-JEV to these children with pre-existing neutralizing JE antibody titers was safe and resulted in substantial boosting of antibody levels. These results may inform other countries in Asia considering switching from IMBV to now WHO-prequalified CD-JEV vaccine to combat this disease of public health importance.
减毒活日本脑炎SA 14-14-2疫苗（CD-JEV）在先前接种过灭活鼠脑源性日本脑炎疫苗（IMBV）的儿童中的表现尚不清楚。我们评估了在斯里兰卡给2岁和5岁儿童接种CD-JEV的安全性和免疫原性。
在斯里兰卡科伦坡地区进行的这项开放标签、单臂试验中，分别先前接种过两剂和三剂IMBV的2岁和5岁一般健康儿童皮下接种一剂CD-JEV。对参与者在接种疫苗后一年进行不良事件监测。使用日本脑炎蚀斑减少中和试验在接种疫苗前、接种后28天和365天评估血清中和抗体反应，并将其表征为血清阳转参与者的比例。血清阳转定义为基线滴度<1:10的参与者中达到被认为具有血清保护作用的滴度（⩾1:10），或基线滴度⩾1:10的参与者中滴度至少升高4倍。
在305名接种CD-JEV的儿童中，294名被纳入免疫原性的初步分析。接种疫苗前，144/147（98.0%）的2岁儿童和146/147（99.3%）的5岁儿童具有血清保护水平。接种疫苗后28天，79/147 [53.7%（95%CI，45.3 - 62.0）]的2岁儿童和60/147 [40.8%（95%CI，32.8 - 49.2）]的5岁儿童实现了血清阳转。在2岁儿童中，接种疫苗后28天几何平均滴度（GMTs）从697升至3175。在5岁儿童中，GMTs从926升至2776。大多数不良反应为轻度，且没有严重不良事件与研究疫苗接种相关。
给这些预先存在中和性日本脑炎抗体滴度的儿童接种CD-JEV是安全的，并导致抗体水平大幅提高。这些结果可能为亚洲其他考虑从IMBV转向目前世卫组织预认证的CD-JEV疫苗以防治这种具有公共卫生重要性疾病的国家提供参考。
