重组戊型肝炎疫苗原液长期稳定性评价  

Long-term stability of bulk of recombinant hepatitis E vaccine

作　　者：贾媛 迟祥 李铮 宋昊 于爱东 韩顺子 常东英 陈子杨 迟春萍 时成波 曹玉锋 刘照惠 

机构地区：[1]长春生物制品研究所有限责任公司,吉林长春130012 [2]长春博迅生物技术有限责任公司,吉林长春130102

出　　处：《中国生物制品学杂志》2017年第12期1233-1237,1273,共6页Chinese Journal of Biologicals

基　　金：吉林省科技发展计划项目(20130204014YY);吉林省产业技术研究与开发项目(2009003)

摘　　要：目的评价重组戊型肝炎疫苗原液的长期稳定性。方法将连续3批重组戊型肝炎疫苗原液置(-20±2)℃保存12个月,分别于第0、3、6、9和12月取样,依据《中国药典》第三部和第四部(2015版)和《重组戊型肝炎疫苗制造及检定规程(暂定)》规定进行无菌检查、蛋白含量、纯度、相对分子质量、等电点和细菌内毒素检测及紫外光谱扫描;第6和12月,分别将3批原液配制成疫苗进行效力测定。结果 3批疫苗原液在各时间点无菌检查均为阴性,细菌内毒素含量均小于5 EU/ml,蛋白含量在3.47~3.81 mg/ml,单体及二聚体总量在96.0%以上,二聚体占总蛋白的85%~100%,单体相对分子质量为19 500~19 700,等电点检查主区带在4.05~5.80之间,紫外光谱扫描最大吸收峰在(278±3)nm,3批原液第6和12月的效力ED_(50)值≤1.0μg,均符合暂定制检规程。结论重组戊型肝炎疫苗原液在(-20±2)℃可稳定存放12个月,本研究为原液的存放效期提供了可靠的数据支持。Objective To evaluate the long-term stability of recombinant hepatitis E vaccine（rHEV）. Methods Three consecutive batches of bulk of r HEV were stored at（-20 ± 2）℃ for 12 months, from which samples were taken at months0, 3, 6, 9 and 12, tested for sterility, and determined for protein content, purity, relative molecular mass, isoelectric point and bacterial endotoxin, and subjected to ultraviolet spectrometry according to the requirements in Chinese Pharmacopoeia（Volumes Ⅲ and Ⅳ, 2015 edition）and Requirements for Recombinant Hepatitis E Vaccine（Draft）. The three batches of bulk were prepared into vaccine for potency test at months 6 and 12. Results Three batches of bulk were negative in sterility test at various time points, while the bacterial contents were less than 5 EU/ml, the protein contents were 3. 47 ~3. 81 mg/ml, the total contents of monomers and dimmers were more than 96. 0%, the dimmer contents were 85% ~100% of total protein, the relative molecular masses of monomers were 19 500 ~ 19 700, the isoelectric points of main bands were 4. 05 ~ 5. 80, the maximum adsorption peaks of ultraviolet spectrometry appeared at wavelength of（278 ±3） nm, the ED_（50） values at months 6 and 12 were less than 1. 0 μg, which met the requirements for preparation and control tests. Conclusion The bulk of r HEV may be stored at（-20 ± 2） ℃ for 12 months. The study provided a reliable data support for the validity period of the bulk.

关 键 词：重组戊型肝炎疫苗 原液 长期稳定性 

分 类 号：R373.21[医药卫生—病原生物学] R392.33[医药卫生—基础医学]