不同批次肠道病毒71型(EV71)灭活疫苗的一致性分析  

Consistency of various batches of inactivated enterovirus 71 vaccine

作　　者：张莹[1] 刘龙丁[1] 董承红[1] 王丽春[1] 廖芸[1] 郭磊[1] 王晶晶[1] 梁燕[1] 冯敏[1] 崔伟[1] 李琦涵[1] 

机构地区：[1]中国医学科学院北京协和医学院医学生物学研究所云南省重大传染病疫苗研发重点实验室,云南昆明650118

出　　处：《中国生物制品学杂志》2015年第3期223-227,232,共6页Chinese Journal of Biologicals

基　　金：863计划(2012AA02A404);重大新药创制(2012ZX09101319-002);云南省技术创新人才培养(2014HB066)

摘　　要：目的分析不同批次的肠道病毒71型（enterovirus 71,EV71）灭活疫苗（人二倍体细胞）全程免疫后免疫原性及安全性的一致性。方法检测3批EV71灭活疫苗成品的抗原含量、游离甲醛含量、铝含量、内毒素含量、抗生素残留量,并免疫动物检测异常毒力及效力。采用随机、双盲的方法,将3批疫苗于第0、28天分别免疫900名6~72月龄的受试人群。于接种前（第0天）、完成2剂疫苗接种后28天（第56天）,采集静脉血,分离血清,采用微量细胞病变法检测EV71中和抗体（neutralizing antibody,Nab）效价;于每次接种后30 min内记录即时反应,每剂接种后0~7 d内记录各种征集性局部和全身症状,0~28 d内记录非征集性不良反应事件,并在整个观察期间报告严重不良反应事件。结果 3批EV71灭活疫苗成品的各项检定结果均在合格范围内。经2剂EV71灭活疫苗全程免疫后,20120101、20120102和20120203批疫苗受试者的抗体阳转率分别为98.00%、95.67%和98.67%,易感人群（Nab〈1∶8）免后抗体阳转率分别为96.45%、92.44%和97.60%,非易感人群（Nab≥1∶8）免后抗体水平的4倍增长率分别为67.94%、65.63%和71.43%;免后抗体GMT分别为283.79、231.48和285.78,组间差异均无统计学意义（P均〉0.05）。3批疫苗诱导的与疫苗相关的不良反应及严重不良反应事件,组间差异无统计学意义（P〉0.05）。结论通过比较3批疫苗的各项生产质量控制指标及其诱导的抗体水平,证实该疫苗的生产工艺较稳定。Objective To investigate the consistency of immunogenicity and safety of full course of vaccination with inac-tivated enterovirus 71（EV71） vaccine（human diploid cells） of various batches. Methods Three batches of inactivated EV71 vaccine were determined for antigen content, free formaldehyde content, aluminum content, endotoxin content,residual antibiotic content, abnormal toxicity and potency. A random and double-blind trial was carried out on the three batches of vaccine in 900 children at ages of 6 ~ 72 months. The children were immunized on days 0 and 28, of whom serum samples were collected on days 0（before immunization） and 56, and determined for neutralizing antibody titer against EV71 by micro-CPE method. Immediate reactions were recorded within 30 min, while the recruiting local and systemic symptoms within 0 ~ 7 d, and the non-recruiting adverse reactions within 0 ~ 28 d, after each dose. The severely adverse events were reported during the whole observation. Results All the control test results of three batches of final products of inactivated EV71 vaccine were within the range of qualification. The antibody positive conversion rates of children after immunization with two doses of inactivated EV71 vaccine of Lots 20120101, 20120102 and 20120203 were98. 00%, 95. 67% and 98. 67%, while those of susceptible children（with neutralizing antibody titers of less than 1 ∶ 8）were 96. 45%, 92. 44% and 97. 60%, respectively. However, the 4-fold increasing rates of antibody titers of unsusceptible children（with neutralizing antibody titers of not less than 1 ∶ 8）after immunization with the three batches were 67. 94%,65. 63% and 71. 43%, while the GMTs of antibody were 283. 79, 231. 48 and 285. 78, respectively, which showed no sig-nificant difference（each P〉0. 05）. The adverse reactions and severely adverse events induced by the vaccine of the three batches showed no significant difference（P〉0. 05）. Conclusion The production procedure of inactivated EV71 vaccine was stable as pr

关 键 词：EV71灭活疫苗 人二倍体细胞 免疫原性 安全性 一致性 

分 类 号：R373.2[医药卫生—病原生物学] R392-33[医药卫生—基础医学]