北京株(VZV84-7)水痘病毒在麻疹-腮腺炎-风疹-水痘联合减毒活疫苗中的稳定性

Stability of varicella virus VZV84-7 strain in live attenuated measles-mumps-rubella-varicella combined vaccine

目的观察北京株(VZV84-7)水痘病毒在麻疹-腮腺炎-风疹-水痘(measles-mumps-rubella-varicella,MMRV)联合减毒活疫苗中的稳定性。方法将4批MMRV联合减毒活疫苗成品分别置37℃保存4周、2~8及-15^-20℃保存24个月,采用蚀斑形成单位(plaque forming unit,PFU)试验检测不同时间点疫苗中水痘病毒滴度。将水痘病毒原液于-80℃反复冻融1、2、3次后,分别与麻疹、腮腺炎、风疹各单价疫苗原液按一定比例配制成MMRV联合减毒活疫苗,进行冻干,采用PFU试验分别测定冻干前、冻干后基础水痘病毒滴度及冻干后于37℃热稳定1周的水痘病毒滴度。结果 4批MMRV联合减毒活疫苗成品于37℃保存4周后,水痘病毒滴度下降范围为0.5~0.7 lg PFU/ml;于2~8℃保存24个月,水痘病毒滴定最高达4.6 lg PFU/ml,最低为4.4 lg PFU/ml;于-15^-20℃放置24个月,水痘病毒滴度基本保持不变,均达合格标准(不低于3.6 lg PFU/ml)。水痘病毒原液经1、2、3次冻融后制备的MMRV,通过37℃热稳定1周,水痘病毒滴度分别为4.9~4.6、4.6~4.4、4.5~4.3 lg PFU/ml,均达到合格标准(不低于3.6 lg PFU/ml)。结论北京株(VZV84-7)水痘病毒在MMRV联合减毒活疫苗中稳定性良好。

Objective To observe the stability of varicella virus VZV84-7 strain in live attenuated measles-mumps-rubellavaricella（MMRV）combined vaccine. Methods Four batches of MMRV were stored at 37 ℃ for 4 weeks, while at 2 - 8and-15 --20 ℃ for 24 months separately, and determined for varicella virus titers at various time points by plaque forming unit（PFU） assay. Bulk of varicella virus was subjected to repeat freeze-thawing at-80 ℃ for 1, 2 and 3 times,then mixed with measles, mumps and rubella viruses at certain ratios. The prepared MMRV vaccine was lyophilized, of which the basic varicella virus titers before and after lyophilization as well as the varicella virus titer after storage at 37 ℃for one week were determined by PFU assay. Results The varicella virus titers of four batches of MMRV decreased by0. 5 - 0. 7 lgPFU / ml after storage at 37 ℃ for 4 weeks. However, after storage at 2 - 8 ℃ for 24 months, the highest and the lowest varicella virus titers were 4. 6 and 4. 4 lgPFU / ml respectively. After storage at-15 --20 ℃ for 24 months,the varicella virus titer showed no significant change, which was not less than 3. 6 lgPFU / ml. The varicella virus titers of MMRV prepared with the bulks after 1, 2 and 3 cycles of freeze-thawing were 4. 9 - 4. 6, 4. 6 - 4. 4 and 4. 5 -4. 3 lgPFU / ml respectively after storage at 37 ℃ for one weeks, which were not less than 3. 6 lgPFU / ml. Conclusion Varicella virus VZV84-7 strain were highly stable in MMRV.