麻疹-流行性腮腺炎-流行性乙型脑炎联合减毒活疫苗的安全性评价

Safety of Measles,Mumps,and Japanese Encephalitis Combined Attenuated Live Vaccine

目的进行麻疹-流行性腮腺炎(流腮)-流行性乙型脑炎(乙脑)联合减毒活疫苗(Measles,Mumps and Japanese Encephalitis Combined Attenuated Live Vaccine,M-M-JEV)的安全性评价。方法小鼠急性毒性试验:设M-M-JEV拟用临床剂量的80倍为低剂量,拟用临床剂量的400倍为高剂量,1次皮下注射给药,同时设阴性对照。观察临床症状,检查注射部位、体重、病理学。猴体长期毒性试验:设M-M-JEV拟用临床剂量为低剂量,拟用临床剂量的5倍为高剂量,2次皮下注射给药,同时设阴性对照及麻疹减毒活疫苗、流腮减毒活疫苗和乙脑减毒活疫苗对照。观察临床症状,检查注射部位、体温、体重、心电图、血液学、血清生物化学、摄食量、尿液、眼科学以及血清中和抗体(Neutralizing Antibody,NA)的变化情况,大体病理学和组织病理学检查。结果各项观察指标及检查结果均与对照疫苗或阴性对照相似,相关数据与对照疫苗或阴性对照组比较差异无统计学意义,未见其他明显毒副作用,第1次给药后4周,麻疹病毒NA、流腮病毒NA及乙脑病毒NA水平与对照单价疫苗比较差异均无统计学意义。结论M-M-JEV表现出与单价疫苗相似的安全性和免疫原性。

Objective To evaluate the safety of measles, mumps, and Japanese encephalitis （JE） com- bined attenuated live vaccine （M-M-JEV）. Methods For the mouse acute toxicity test, the low dose was 80 times the clinically-used dose and the high dose was 400 times clinically-used dose. A single subcutaneous injection was administrated to the study groups; no vaccine was administered to the negative control group of mice. An observation index was used to record clinical symptoms, the injection site, body weight, and pathological examination results. For the monkey long-term toxicity test,the low dose was the same as a clinically-used dose, and a high dose was 5 times the clinically-used dose. Injections were administrated subcutaneously. The comparison groups included a measles live attenuated vaccine group, a mumps attenua- ted live vaccine group, a JE attenuated Live Vaccine （JEV） group, and a negative control. An observation index included clinical symptoms, injection site evaluation, body weight, temperature, electrocardiogram, hematology, blood biochemistry, food intake, urinalysis, ophthalmological evaluation, serum neutralizing antibody（NA）, gross pathology, and histopathologieal examination. Results The observation indexesshowed that there were no significant differences from the control groups. There were no obvious side effects. NA levels of mumps, measles, and JE were not significantly different from the monovalent vaccine groups. Conclusion M-M-JE vaccine has similar safety and immunogenicity compared with monovalent vaccines.