水痘减毒活疫苗无明胶稳定剂的筛选和应用

Screening and application of gelatin-free stabilizer for live attenuated varicella vaccine

目的 研制不含明胶的新型稳定剂,以提高水痘减毒活疫苗的安全性.方法 以现行水痘减毒活疫苗稳定剂配方为基础,去除明胶,配制4种不同的新型稳定剂（B、C、D、E配方）.用无明胶稳定剂制备水痘减毒活疫苗,并将制备的无明胶稳定剂疫苗（B、C、D、E疫苗）与现行的含明胶稳定剂疫苗（作为对照的A疫苗）进行比较,确定最佳稳定剂配方.结果 疫苗成品于37℃放置7d后,A、B、C、D、E疫苗的相关质量指标均符合《水痘减毒活疫苗注册标准》的要求,病毒滴度分别为3.6、3.5、3.3、3.3、3.3 lgPFU/0.5 ml,但C、D、E疫苗的病毒滴度已降至临界值.疫苗成品于2～8℃放置24个月后,A、B、C、D、E疫苗的病毒滴度分别为3.4、3.4、3.2、3.0、2.8 lgPFU/0.5 ml,其中C、D、E疫苗的病毒滴度已低于规定的标准（3.3 lgPFU/0.5 ml）,仅B疫苗的相关质量标准符合规定的要求,且与A疫苗（对照）没有差异.结论 去除明胶的B配方稳定剂对水痘病毒有较好的保护作用.

Objective To develope new gelatin-free stabilizers in order to improve the safety of live attenuated varicella vaccine,Methods Based on the current stabilizer formula of live attenuated varicella vaccine,four new stabilizers （B,C,D,E formulas） were formulated by removing gelatin.Vaccines without gelatin （B,C,D,E vaccines） were prepared with the formulated gelatin-free stabilizers and compared with the current live attenuated varicella vaccine with gelatin （A vaccine as control）.The optimized stabilizer formula was determined.Results After 7 days at 37 ℃,the relevant qualities of all vaccines conformed with the requirement of Registration Criteria of Live Attenuated Vaccine Varicella,and the virus titers of A,B,C,D,E vaccines were 3.6,3.5,3.3,3.3 and 3.3 lgPFU/0.5 ml,respectively,but the virus titers of C,D,E vaccines have dropped to critical value.After 24 months at 2-8 ℃,the virus titers of A,B,C,D,E vaccines were 3.4,3.4,3.2,3.0 and 2.8 lgPFU/0.5 ml,respectively.Among the four vaccines without gelatin,the virus titers of C,D,E vaccines have been below the requirement （3.3 lgPFU/0.5 ml）,only B vaccine met the requirement and was the same as A vaccine.Conclusion The B formula stabilizer without gelatin has better protection for varicella virus.