新车间生产的乙型脑炎减毒活疫苗免疫原性的批间一致性及其对旧车间产品的非劣效性  

Lot-to-lot consistency of immunogenicity of live attenuated Japanese encephalitis vaccine manufactured in a new facility and non-inferiority with respect to product in old facility

作　　者：张磊[1] 刘丹青[2] 王斌冰[2] 陆志坚[2] 罗献伟[2] 周淑洁[2] 王晓萍[3] 马尔健[3] 王蓓[3] 方大春[4] 曹多志[4] 杨锟[4] 陈海琴[4] 周本立[1] 罗静[1] 姚亚夫[1] 

机构地区：[1]成都生物制品研究所有限责任公司,四川成都610023 [2]安徽省疾病预防控制中心,安徽合肥230601 [3]合肥市疾病预防控制中心,安徽合肥230061 [4]马鞍山市疾病预防控制中心,安徽马鞍山243000

出　　处：《中国生物制品学杂志》2016年第6期616-619,622,共5页Chinese Journal of Biologicals

摘　　要：目的验证新车间生产的不同批次乙型脑炎减毒活疫苗免疫原性的批间一致性及其对旧生产车间产品的非劣效性。方法在安徽省合肥市及马鞍山市招募1 723名未接种过乙脑疫苗,无乙型脑炎病史的8-12月龄儿童,随机、双盲法分为4组,分别接种旧生产车间生产的1批及新车间的3批乙型脑炎减毒活疫苗。采集免疫前及免疫后28 d的静脉血,分离血清,采用50%噬斑减少中和抗体试验法检测血清中抗乙型脑炎病毒中和抗体效价,比较不同批次及不同车间生产的疫苗的血清保护率,并对其免疫原性的等效性及非劣效性进行统计学分析,同时评价其安全性。结果 4批疫苗的抗乙脑中和抗体血清保护率为90.14%-92.93%,抗乙型脑炎病毒中和抗体效价的GMT为142.40-191.07,新车间生产的3批疫苗两两比较血清保护率差异的95%可信区间的上、下限均在预设的±10%区间内,新车间生产的疫苗总血清保护率与旧车间生产的疫苗的差异区间下限不超过-10%。4批疫苗的安全性均良好。结论新车间生产的不同批次乙型脑炎减毒活疫苗免疫原性具有良好的批间一致性,且新车间生产的疫苗对旧车间生产的疫苗具有非劣效性。Objective To verify the lot-to-lot consistency of immunogenicity of live attenuated Japanese encephalitis（JE）vaccine manufactured in a new facility as well as non-inferiority with respect to an earlier product manufactured in old facility. Methods A four-arm, double-blind, randomized controlled trial was performed in Hefei and Maanshan Cities in Anhui Province, China. A total of 1 723 healthy infants at ages of 8 ~ 12 months were enrolled and randomly divided into four groups, and immunized respectively with one batch of vaccine manufactured in old facility and three batches of vaccines manufactured in a new facility. Blood samples were collected before and 28 d after immunization, and determined for neutralizing antibody titer against JE virus by 50% plaque reduction neutralization test（PRNT）. The seroprotection rates of four groups were compared. The consistency of immunogenicity of vaccine manufactured in a new facility as well as non-inferiority with respect to vaccines manufactured in old facility were analyzed statistically, while the safeties were evaluated. Results The seroprotection rates of four batches of vaccine were 90. 14% ~ 92. 93%, while the GMTs of neutralizing antibodies against JE virus were 142. 40 ~ 191. 07. Both the upper and lower limits of 95% confidence intervals（CIs）of differences between the seroprotection rates of three batches of vaccine manufactured in new facility were within ± 10% of the pre-specified margin. However, the lower limit of 95% CIs of difference between the seroprotection rate of vaccines manufactured in new facility was not more than-10% from those in new facility. All the four batches of vaccine showed high safeties. Conclusion The vaccines of different batches manufactured in new facility showed good lot-to-lot consistency of immunogenicity. However, the vaccines manufactured in new facility showed non-inferiority as compared with those in old facility.

关 键 词：乙型脑炎减毒活疫苗 免疫原性 批间一致性 非劣效性 

分 类 号：R373.31[医药卫生—病原生物学] R392-33[医药卫生—基础医学]