细胞工厂在麻腮风系列疫苗生产中的应用

Application of cell factory in production of a series of MMR vaccine

目的利用细胞工厂培养麻疹、腮腺炎和风疹病毒,并制备麻腮风各单价及联合疫苗。方法应用40层细胞工厂培养原代鸡胚细胞和2BS细胞,制备麻疹、腮腺炎和风疹病毒原液(同时以15 L转瓶培养工艺作为对照),并制备麻腮风各单价及联合疫苗,按照《中国药典》三部(2015版)方法进行病毒滴度检测。结果细胞工厂制备的麻疹、腮腺炎和风疹病毒原液滴度分别为大于5.2、6.1和5.7 lgCCID_(50)/mL,高于转瓶工艺,且符合《中国药典》三部(2015版)相关规定;1个40层细胞工厂制备的病毒原液量相当于1个转瓶的4至8倍,产量较高。细胞工厂制备的多批次麻腮风各单价及联合疫苗的病毒滴度均符合《中国药典》三部(2015版)相关标准,且病毒滴度热稳定性下降均不超过1个lg。结论利用细胞工厂制备麻腮风各单价及联合疫苗的工艺稳定,重复性好,质量可控,可用于规模化生产。

Objective To culture measles, mumps and rubella viruses in cell factory and prepare the relevant monovalent and combined vaccines. Methods The bulks of measles, mumps and rubella viruses were prepared by culture of primary chick embryo cells and 2BS cells in 40-layer cell factory, using those cultured in 15 L miler bottle as control, based on which the relevant monovalent and combined vaccines were prepared and determined for titer according to the requirements in Chinese Pharmacopoeia （Volume m, 2015 edition）. Results The titers of bulks of measles, mumps and rubella viruses cultured in cell factory were 5. 2, 6. 1 and 5. 7 lgCCID50/mL respectively, which were significantly higher than those cultured in roller bottle and met the requirements in Chinese Pharmacopoeia （Volume ]U, 2015 edition）. The yields of bulks prepared by a cell factory were equivalent to 4 - 8 times of those by culture in roller bottle. All the titers of monovalent and combined vaccines prepared by cell factory met the requirements in Chinese Pharmacopoeia （Volume II1, 2015 edition）, and decreased by not more than 1 lg in heat stability test. Conclusion The process for production of monovalent and combined measles, mumps and rubella vaccines by cell factory was stable, reproducible and controllable, which might used for large-scale production.