生物反应器制备森林脑炎灭活疫苗(Vero细胞)的免疫原性及安全性评价  

Immunogenicity and safety of inactivated vaccine against tick-borne encephalitis(Vero cells)prepared by using bioreactor

作　　者：梅可佳 刘岩松 张颖 刘旭善 张朔 毕婷婷 谢继莹 王伟善 孙宏亮 MEI Ke-jia;LIU Yan-song;ZHANG Ying;LIU Xu-shan;ZHANG Shuo;BI Ting-ting;XIE Ji-ying;WANG Wei-shan;SUN Hong-liang(Changchun Institute of Biological Products Co.,Ltd.,Changchun 130062,Jilin Province,China)

机构地区：[1]长春生物制品研究所有限责任公司,吉林长春130062 [2]长沙生殖医学医院,湖南长沙410205

出　　处：《中国生物制品学杂志》2020年第10期1089-1092,共4页Chinese Journal of Biologicals

基　　金：国家科技部重大新药创制项目(2013ZX09402302-205)。

摘　　要：目的评价生物反应器工艺制备森林脑炎灭活疫苗(Vero细胞)在动物体内的免疫原性及安全性。方法采用生物反应器培养Vero细胞,感染森林脑炎病毒(tick-borne encephalitis virus,TBEV),连续收获,经Sepharose 4FF柱层析纯化后,制备森林脑炎灭活疫苗,免疫昆明小鼠,检测疫苗在动物体内的免疫原性;通过疫苗接种豚鼠主动过敏性试验、ICR小鼠急性毒性试验、新西兰兔局部刺激性试验,评价疫苗在动物体内的安全性。结果制备的森林脑炎灭活疫苗(Vero细胞)对小鼠的免疫保护指数大于5.0×10^5,符合《中国药典》三部(2015版)标准。豚鼠主动过敏试验无豚鼠出现过敏性反应;急性毒性试验ICR小鼠未见明显毒性反应;局部刺激试验新西兰兔注射部位局部大体观察未见明显异常改变。结论生物反应器工艺制备的森林脑炎灭活疫苗(Vero细胞)具有良好的免疫原性和安全性。Objective To evaluate the immunogenicity and safety of inactivated tick-borne encephalitis vaccine(Vero cells)prepared by using bioreactor technique in animals.Methods Vero cells were cultured in bioreactor and infected with tick-borne encephalitis virus(TBEV).The cultured virus was harvested and purified by Sepharose 4 FF column chromatography to prepare inactivated tick-borne encephalitis vaccine,of which the immunogenicity was evaluated by immunization in Kunming mice,while the safety by active allergy test in guinea pigs,acute toxicity test in ICR mice and local irritation test in New Zealand rabbits.Results The immune protection index of prepared vaccine to mice was more than 5.0×10^5,which met the requirements in Chinese Pharmacopoeia(VolumeⅢ,2015 edition).No allergic reactions were observed in active allergy test in guinea pigs,while no obviously toxic reactions in acute toxicity test in ICR mice.However,no abnormal changes in injection sites were observed in gross observation rabbits in local irritation test.Conclusion The inactivated tick-borne encephalitis vaccine prepared by using bioreactor technique showed good immunogenicity and safety.

关 键 词：森林脑炎灭活疫苗 VERO细胞 生物反应器 免疫原性 安全性 

分 类 号：R392[医药卫生—免疫学]