戊型肝炎疫苗效力国家参考品的制备

Preparation of Chinese national potency reference for hepatitis E vaccine

目的制备戊型肝炎疫苗(简称戊肝疫苗)效力国家参考品,用于戊肝疫苗效力的质量控制。方法选取1批戊肝疫苗为候选参考品原料,加入经筛选的冻干保护剂,分装、冻干后制备为候选参考品,进行均匀性和稳定性考察,并分发给4个实验室进行协作标定和适用性研究。结果选择5%海藻糖+2%右旋糖酐作为冻干保护剂制备候选参考品。候选参考品的分装精度为0.7%;抗原含量均匀性变异系数(coefficient of variation,CV)为9.0%;铝含量均匀性CV为4.0%。水分含量为1.7%。候选参考品具有较好的加速稳定性和复溶稳定性。协作标定共获得18个有效数据,结果显示候选参考品半数有效量(median effective dose,ED50)均值为0.15μg(95%置信区间为0.12~0.18μg),实验室内CV为30.8%~64.2%,实验室间CV为32.6%。2家实验室自行研制的戊肝疫苗与候选参考品均表现出良好的剂量效应关系,阳转率均随疫苗抗原含量减少而降低,曲线变化趋势相近。结论首次制备了戊肝疫苗效力国家参考品(300031-201801),用于戊肝疫苗效力ED50检测质量控制。

Objective To prepare the hepatitis E vaccine national potency reference for the quality control of hepatitis E vaccine.MethodsA batch of hepatitis E vaccine was selected as the row material,and the screened lyoprotectant was added.After aliquot and freeze-drying,it was prepared as candidate reference material,and the homogeneity and stability were investigated,which was distributed to four laboratories for collaborative calibration and applicability study.Results The 5%trehalose+2%dextran was selected as the lyoprotectant to prepare the candidate reference material.The aliquot accuracy of candidate reference material was 0.7%;The coefficient of variation(CV)of antigen content homogeneity was9.0%;The CV of aluminum content homogeneity was 4.0%.Moisture content was 1.7%.The candidate reference material showed good acceleration stability and reconstituted stability.A total of 18 valid data were obtained from the collaborative calibration.The results showed that the average value of median effective dose(ED50)was 0.15μg(95%confidence interval of 0.12~0.18μg)with the intra-laboratory CV of 30.8%~64.2%,and the inter-laboratory CV of 32.6%.Two hepatitis E vaccines produced by two laboratories themselves and the candidate reference material showed good dose-response relationship,of which the seroconversion rate decreased with the decrease of vaccine antigen content and the curve change trend was similar.ConclusionThe first Chinese national potency reference for hepatitis E vaccine(300031-201801)was prepared,which can be used for the quality control of potency ED50detection of hepatitis E vaccine.