目的  建立麻疹、腮腺炎、风疹和水痘（measles，mumps，rubella and varicella，MMRV）联合减毒活疫苗的生产工艺和检定方法。方法  采用麻疹病毒沪-191株、腮腺炎病毒S79株、风疹病毒BRDⅡ株、水痘-带状疱疹病毒北京84-7株，在原代鸡胚细胞或人胚肺二倍体细胞2BS株中制备高滴度疫苗病毒原液。观察4种原液按不同比例稀释配制后病毒的滴度变化和相互干扰现象，确定MMRV疫苗中4种原液的配制比例，并筛选适宜保护剂，建立最佳冻干工艺。同时，建立MMRV联合减毒活疫苗的检定方法。采用t检验对结果进行比较。 结果   选择最佳配制比例、保护剂和冻干工艺制备出连续多批MMRV疫苗，按国家药典要求检定全部合格。其中连续3批疫苗经国家检定机构检定合格：麻疹病毒基础滴度和37 ℃放置7 d后的滴度分别≥3.9和≥3.5 lg半数细胞培养感染量（50% cell culture infective dose，CCID₅₀）/ml，腮腺炎病毒≥5.0和≥4.7 lgCCID₅₀/ml，风疹病毒≥5.0和≥4.8 lgCCID₅₀/ml，水痘病毒≥4.5和≥4.4 lg空斑形成单位/ml。用建立的方法检测MMRV疫苗，结果4种病毒滴度实测值与理论值之间的差异无统计学意义（t值为0.149～1.838，P值均>0.05）。 结论  建立了稳定、可行的MMRV疫苗生产工艺和检定方法。

Objective  To establish the production process and titration method of a live measles, mumps, rubella and varicella (MMRV) combined vaccine.  Methods   Four high-titer virus bulks were prepared using measles virus strain Shanghai-191, mumps virus strain S79, rubella virus strain BRD Ⅱand varicella-zoster virus strain Beijing 84-7 cultured in primary chicken embryo cell or human embryo lung diploid cell 2BS. The titer change and mutual interference of 4 kinds of viruses were observed after preparation with different dilution ratios. The appropriate protective agent was screened and the best freeze-drying condition determined. Meanwhile, the titration method of live MMRV vaccine was established. The results were compared with t-test.  Results  Several consecutive batches of MMRV vaccine were prepared with the best dilution ratio, protective agent and freeze-drying process and met the requirements in Chinese pharmacopoeia. Among which, 3 consecutive batches were determined by national verification institution. The virus titers before and after 7 days at 37 ℃ were as follows: measles ≥3.9 and ≥3.5 lg 50% cell culture infective dose (CCID₅₀）/ml, mumps ≥5.0 and ≥4.7 lgCCID₅₀/ml, rubella ≥5.0 and ≥4.8 lgCCID₅₀/ml, varicella ≥4.5 and ≥4.4 lg plaque-forming unit/ml. Determined by the establish method (t=0.149-1.838, p>0.05), there was no significant difference between the measured and theoretical titers of 4 kind viruses in MMRV vaccine. Conclusion  The production process and titration method established are stable and feasible.