低血清培养基在水痘减毒活疫苗生产中的应用

目的 应用低血清培养基在水痘减毒活疫苗生产过程中进行细胞和病毒培养,观察培养效果,验证其对疫苗生产的适用性。方法 采用低血清培养基培养MRC-5细胞和水痘病毒Oka株,以传统培养基的生产为对照,比较细胞生长、病毒感染情况及原液病毒滴度和牛血清白蛋白残留量。采用t检验对结果进行比较。结果 在相同工作细胞库细胞复苏的情况下,低血清培养基与传统培养基培养的细胞和病毒形态,没有明显的差异。低血清培养基与传统培养基培养得到的水痘病毒原液病毒滴度均为5.0~5.1 lg噬斑形成单位/ml,差异无统计学意义(t=1.00,P>0.05);但低血清培养基生产的水痘病毒原液中牛血清白蛋白残留量(12~19 ng/ml)显著低于传统培养基生产的(39~46 ng/ml)(t=8.51,P<0.05)。结论 在水痘减毒活疫苗生产过程中应用低血清培养基未影响病毒滴度,但牛血清白蛋白残留量明显降低,减少了因牛源性成分引起疫苗不良反应的风险,可提高疫苗质量,适用于水痘减毒活疫苗的生产。

Application of low serum medium in live attenuated varicella vaccine production

Objective  To culture cells and viruses  in the production process of live attenuated varicella vaccine with low serum medium, and observe the culture effect in order to verify its applicability in vaccine production. Methods  MRC-5 cells and Oka strain of varicella virus were cultured with low serum medium. The cell proliferation, virus infection, as well as virus titer and bovine serum albumin (BSA) residue of the virus stock were inspected and compared with those using traditional medium by t-test. Results  Using the same work cell bank, there was no significant difference in cell and virus morphology between cultures with low serum medium and traditional medium. The virus titers were both 5.0-5.1 lg plaque-forming unit/ml and there was no statistically significant difference (t=1.00, P>0.05). The BSA residue amount of varicella stock with low serum medium（12~19ng/ml） was significantly lower than that with traditional medium  39~46ng/ml）(t=8.51, P<0.05). Conclusions  Using low serum medium in the production process of live attenuated varicella vaccine does not affect the virus titer, but significantly lowers the BSA residue, thus can reduce the risk of vaccine adverse reactions caused by bovine origin. Low serum medium improves the quality of vaccine and is suitable for the production of liver attenuated varicella vaccine.