麻疹减毒活疫苗生产工艺优化  

Optimization of production process of measles attenuated live vaccine

作　　者：孙雅 刘思墨 石婷婷 商雪萌 唐浩博 简哲 邱梅 王刚 SUN Ya;LIU Simo;SHI Tingting;SHANG Xuemeng;TANG Haobo;JIAN Zhe;QIU Mei;WANG Gang(Vaccine Laboratory I,Beijing Institute of Biological Products Co.,Ltd.,Beijing 100176,China)

机构地区：[1]北京生物制品研究所有限责任公司疫苗一室,北京100176

出　　处：《中国医药科学》2023年第7期88-91,共4页China Medicine And Pharmacy

摘　　要：目的调整优化现行麻疹疫苗原液生产工艺,为提高麻疹疫苗及其联合疫苗质量提供参考。方法应用10层细胞工厂(CF10)、三种不同感染复数(MOI)和两种换液次数制备麻疹单价疫苗及其联合疫苗,并取2020年北京生物制品研究所有限责任公司疫苗一室生产的麻腮风联合减毒活疫苗原液商业批的连续三批为对照组,通过比较活细胞数、细胞存活率来确认各组间基线一致性,通过比较麻疹病毒滴度与细胞病变程度、麻腮风成品中麻疹病毒滴度及其热稳后滴度来评估优化后的工艺效果。结果各组细胞悬液所含活细胞数与存活率均符合国家规定,具有较好的基线一致性。其中E组滴度均数和标准差波动幅度较理想,一收滴度为(5.77±0.07)lgCCID_(50)/ml,二收滴度为(6.00±0.08)lgCCID_(50)/ml,原液滴度为(5.97±0.05)lgCCID_(50)/ml,E组病变程度更高、面积更大、分布更均匀,与滴度结果相匹配。热稳试验后各组滴度均有不同程度下降,E组方案制备的MMR中麻疹单基滴度和热稳下降幅度较理想,单基滴度为(4.23±0.07)lgCCID_(50)/ml,热稳后滴度为(4.10±0.04)lgCCID_(50)/ml,均数下降0.13 lgCCID_(50)/ml。结论应用CF10、MOI为0.015、两次换液为本次优化的最佳工艺,可进一步提升疫苗原液质量。Objective To adjust and optimize the current production process of measles vaccine stock solution,so as to provide a reference for improving the quality of measles vaccine and its combined vaccine.Methods The measles monovalent vaccine and its combined vaccine were prepared by applying 10-layer cell factory(CF10),three different multiplicities of infection(MOIs)and two fluid changes,and three consecutive batches of Measles,Mumps and Rubella Combined Vaccine,Live(MMR)stock produced in Vaccine LaboratoryⅠof Beijing Institute of Biological Products Co.,Ltd.in 2020 were taken as the control group.The baseline consistency among the groups was determined by comparing the number of alive cells and cell survival rate,and the effect of the optimized process was evaluated by comparing the titer of measles virus with the degree of cytopathy,and the titer of measles virus in the finished MMR vaccine product with its titer after heat stabilization.Results The number of alive cells and survival rate of cells in the suspensions in all groups were in line with national regulations and had good baseline consistency.The mean and standard deviation of titer fluctuations were acceptable in Group E,with the titer of(5.77±0.07)lgCCID_(50)/ml for first harvested cell suspension,(6.00±0.08)lgCCID_(50)/ml for second harvested cell suspension,and(5.97±0.05)lgCCID_(50)/ml for stock solution.The cytopathy in Group E was of higher degree,larger area and more uniform distribution,which matched with the titer results.The titers of all groups decreased to different degrees after the heat stabilization test,and the decrease ranges of monobasic titers and titers after heat stabilization for measles in MMR prepared with Group E program were acceptable,with a monobasic titer of(4.23±0.07)lgCCID_(50)/ml,a titer of(4.10±0.04)lgCCID_(50)/ml after heat stabilization,and a mean decrease of 0.13 lgCCID_(50)/ml.Conclusion The application of a CF10,MOI of 0.015 and two fluid changes are the best process obtained from this optimization,which can furt

关 键 词：麻疹疫苗 工艺优化 细胞工厂 感染复数 换液次数 

分 类 号：R392.33[医药卫生—免疫学]