无明胶保护剂冻干乙型脑炎灭活疫苗(Vero细胞)稳定性研究

摘要

Objective To observe stability of lyophilized inactivated Japanese encephalitis vaccine (Vero cell) without gelatin.Methods Lactose was used as a substitute for gelatin in the current lyophilized inactivated Japanese encephalitis vaccine.Human albumin contents were increased to 5,10 and 20 g/L,respectively.Three vaccines (A,B and C) were prepared and evaluated by accelerated test (25 ℃ for 24weeks),stability test (37 ℃ for 8 weeks) and long-term stability test (2-8 ℃ for 48 months).Effective antigen content and efficacy (T value) of the vaccines were determined and compared with those of the current vaccine.Results After 24 weeks at 25 ℃,effective antigen contents of A and B vaccines only reduced by 2.2％ and 5.9％,respectively,and T values remained stable; however,the effective antigen and T value of C vaccine reduced by 13.6％ and 5.0％,respectively.After 8 weeks at 37 ℃,effective antigen contents of A,B,C vaccines reduced by 11.2％,13.2％ and 15.2％,T values reduced by 5.8％,9.0％ and 7.2％,respectively.After 48 months at 2-8 ℃,effective antigen contents of A,B,C vaccines reduced by 17.2％,18.4％ and 21.9％,respectively,but the T values complied with the Requirement of Registration Criteria of Lyophilized Inactivated Japanese Encephalitis Vaccine (Vero Cell).In above tests,A and B vaccines were superior or equivalent to the control vaccine.Even though the results of C vaccine were rather different from those of the control vaccine,they all met the requirement.Conclusion The A formula is considered to be the preferred choice based on the high stability of and less human albumin in A vaccine.%目的 观察不含明胶的不同保护剂配方冻干乙型脑炎灭活疫苗(Vero细胞)的稳定性.方法 在现行冻干乙型脑炎灭活疫苗制备工艺的基础上,以乳糖替代明胶,并适当增加人血白蛋白用量至5、10和20g/L,制成A、B、C三个保护剂配方疫苗.对疫苗进行25℃加速试验、37℃热稳定性试验和2～8℃长期稳定性试验,检测疫苗的有效抗原含量和效力(T值),并与现行疫苗(对照)进行比较.结果 三个保护剂配方疫苗于25℃放置24周后,A、B疫苗有效抗原含量仅分别降低2.2％和5.9％,效力稳定；而C疫苗有效抗原含量降低13.6％,效力降低5.0％.37℃放置8周后,A、B、C疫苗有效抗原含量分别降低11.2％、13.2％、15.2％,效力分别降低5.8％、9.0％、7.2％.2～8℃放置48个月后,A、B、C疫苗有效抗原含量分别降低17.2％、18.4％、21.9％,效力均符合《冻干乙型脑炎灭活疫苗(Vero细胞)注册标准》.在上述试验中,A、B疫苗均优于或等于对照疫苗；C疫苗与对照疫苗差异较大,但均符合相关标准.结论 含A配方保护剂的冻干乙型脑炎灭活疫苗稳定性高且白蛋白用量少,因此,建议首选A配方保护剂.