麻疹-流行性乙型脑炎联合减毒活疫苗的安全性评价  

Safety of Measles and Japanese Encephalitis Combined Attenuated Live Vaccine

作　　者：李萍萍[1] 李伟[2] 刘胜[1] 屈哲[2] 齐卫红[2] 贾丽丽[3] 易玲[1] 王月[1] 

机构地区：[1]武汉生物制品研究所有限责任公司,国家联合疫苗工程技术研究中心,湖北武汉430207 [2]中国食品药品检定研究院/国家药物安全评价监测中心,北京100176 [3]中国食品药品检定研究院,北京100050

出　　处：《中国疫苗和免疫》2015年第1期62-67,共6页Chinese Journal of Vaccines and Immunization

基　　金：国家高技术研究发展计划(863计划)重大项目生物和医药技术领域疫苗与抗体工程项目(编号2006AA02A233);生物技术领域疫苗研发关键技术及产品研发项目(编号2012AA02A401)

摘　　要：目的进行麻疹-流行性乙型脑炎(乙脑)联合减毒活疫苗(Measles and Japanese Encephalitis Combined Attenuated Live Vaccine,M-JEV)的安全性评价。方法小鼠急性毒性试验:设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-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3周和4周,麻疹病毒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-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 uated live vaccine （M-JEV）. clinical dose was used as the Methods Acute toxicity low dose and 400 times hi and Japanese encephalitis test in mice： M-JEV 80 （JE） combined atten- times higher than the er than the clinical dose was used as the high dose; doses were given in 1 subcutaneous injection; a negative control was used. We observed clinical symptoms, inspected the injection sites, assessed body weights, and performed pathology examinations. Long term toxicity was tested in monkeys： M-JEV at the clinical dose was used as the low dose and 5 times higher than the clinical dose was used as the high dose; administration was with 2 subcutaneous in- jections; we used a negative control as well as measles vaccine live （MV） and Japanese Encephalitis Vaccine live （JEV） controls. We observed clinical symptoms, and checked the injection sites, tempera- tures, body weights, electrocardiograms, hematology, blood biochemistry, food intake, urine, ophthal- mologic examinations, serum neutralizing antibody tests, gross pathology, and histopathology. Results The observed indexes and test results, compared with the negative control vaccine were similar. There were no statistically significant differences found when compared with the control vaccine groups and thenegative control group. There were no obvious side effects. Three and four weeks after the first dose, measles virus and JE virus neutralizing anti- body levels, compared with control monovalent vaccine groups, showed no statistically significant differences. Conclusion M-JEV has similar safety and immunogenicity as the component mon- ovalent vaccines.

关 键 词：麻疹-流行性乙型脑炎联合减毒活疫苗 安全性评价 长期毒性 免疫原性 局部刺激性 急性毒性 

分 类 号：R186[医药卫生—流行病学] R512.32[医药卫生—公共卫生与预防医学]