利用MODDE软件全因子分析优化乙脑灭活疫苗的纯化工艺  

Optimization of the Purification Platfrom of JE Inactivated Vaccine by the Full Factor Analysis Function of MODDE Software

作　　者：李庆岸 于海 曹鹏 康文哲 LI Qing'an;YU Hai;CAO Peng;KANG Wenzhe(Liaoning Chengda Biotechnology Co.,Ltd.,Shenyang 110179,China)

机构地区：[1]辽宁成大生物股份有限公司,辽宁沈阳110179

出　　处：《生物化工》2022年第6期78-80,共3页Biological Chemical Engineering

摘　　要：目的:通过MODDE软件全因子分析实验方法建立一种乙脑灭活疫苗纯化新工艺,进一步去除乙脑灭活疫苗中细胞残留DNA。方法:将传统的Sepharose 6 Fast Flow层析所获得的初步纯化液作为样品,进行Sartobind Q膜层析,选取上样量、盐浓度、pH、流速4个因子为输入变量,以乙脑疫苗抗原回收率、细胞残留DNA去除率为输出响应值,使用全因子DOE模型进行实验。结果:在实验参数范围内[上样量(40~100 mL)、盐浓度(0.3~0.7 mol/L)、pH(6.0~8.0)、流速(1~20 mL/min)],增加Sartobind Q膜层析的样品细胞残留DNA低于每剂50 pg,去除率在90%以上。结论:通过应用DOE实验设计,找到Sartobind Q膜合适的工艺设计空间,有效去除乙脑灭活疫苗中的细胞残留DNA,提高疫苗临床应用的安全性。Objective:To establish a new purification process for inactivated JE vaccine by the full factor analysis function of MODDE software,and further remove residual DNA in the inactivated JE vaccine.Methods:The initial purified liquid obtained by traditional Sepharose 6 Fast Flow chromatography is used as the sample for Sartobind Q membrane chromatography.Four factors including sample loading,salt concentration,pH and flow rate are selected as the input variables.The antigen recovery rate of JE vaccine and the removal rate of residual DNA of cells are used as the output response values.Experiments are carried out using the full-factor DOE model.Results:In the range of experimental parameters,sample loading 40~100 mL,salt concentration 0.3~0.7 mol/L,pH 6.0~8.0 and flow rate 1~20 mL/min,the samples after Sartobind Q film chromatography residual DNA is reduced to below 50 pg per dose,the removal rate is above 90%.Conclusion:Through DOE experimental design,the appropriate process design space of Sartobind Q film is found to effectively remove residual DNA in the cell of JE inactivated vaccine and improve the safety of vaccine clinical application.

关 键 词：DOE 乙脑灭活疫苗 抗原回收率 细胞DNA残留量 

分 类 号：R186.3[医药卫生—流行病学] R512.32[医药卫生—公共卫生与预防医学]