结核分枝杆菌亚单位疫苗Ag85b-ESAT-6+Hsp65-IL-2的安全性评价研究  

Safety evaluation of Ag85b-ESAT-6+Hsp65-IL-2 subunit vaccine of Mycobacterium tuberculosis

作　　者：路延之[1] 王丽梅[1] 康健[1] 杨锐[2] 张鑫[2] 姚庆港 柏银兰[1] 徐志凯[1] 

机构地区：[1]第四军医大学微生物学教研室,西安710032 [2]第四军医大学学员旅,西安710032

出　　处：《中国人兽共患病学报》2016年第11期945-951,共7页Chinese Journal of Zoonoses

基　　金：国家"十二五"科技重大专项课题(No.2012ZX10003008-007);国家自然科学面上项目(No.81371774和No.81671638);第四军医大学本科生导师(No.2016011)联合资助~~

摘　　要：目的评价结核分枝杆菌亚单位疫苗Ag85b-ESAT-6+Hsp65-IL-2在小鼠和豚鼠体内的安全性。方法小鼠慢性毒性实验:C57BL/6J小鼠间隔2周、皮下3次注射100μg亚单位疫苗(Ag85b-ESAT-6和Hsp65-IL-2各50μg),观察临床症状表现和器官病理学改变。小鼠急性毒性实验:C57BL/6J小鼠皮下注射100μg亚单位疫苗(Ag85b-ESAT-6和Hsp65-IL-2各50μg),观察小鼠临床症状、体重、摄食摄水量、器官的脏器系数和病理学表现。豚鼠全身过敏实验:Hartley豚鼠间隔2d、皮下3次注射1 000μg、100μg、10μg亚单位疫苗(Ag85b-ESAT-6和Hsp65-IL-2均按质量1∶1混合),16d后用二倍剂量足背静脉注射激发,观察体重变化和全身过敏症状。结果小鼠慢性毒性实验表明,亚单位疫苗多次注射后不引起临床症状和病理损伤;小鼠急性毒性实验表明,亚单位疫苗对小鼠不产生临床症状,对小鼠体重、摄食摄水量、脏器系数、器官病理学改变影响无统计学意义;豚鼠全身过敏实验表明,疫苗短期多次致敏对豚鼠的体重无明显影响,低剂量疫苗不引起豚鼠产生全身过敏反应。结论亚单位疫苗Ag85b-ESAT-6+Hsp65-IL-2在小鼠和豚鼠体内均表现出良好的安全性,可用于进一步TB预防和治疗性疫苗的研制。To evaluate the safety of Ag85b-ESAT-6＋Hsp65-IL-2subunit vaccine of Mycobacterium tuberculosis（Mtb）,chronic toxicity and acute toxicity test on mice and systemic anaphylaxis test on guinea pigs were conducted.In chronic toxicity test,50μg Ag85b-ESAT-6＋50μg Hsp65-IL-2were injected subcutaneously to C57BL/6Jmice 3times at the interval of 2weeks.The clinical symptoms and pathology of organs were observed.In acute toxicity test,100μg subunit vaccine（50μg Ag85b-ESAT-6＋50μg Hsp65-IL-2）was injected once subcutaneously to C57BL/6J mice.The clinical symptoms,body weights changes,food consumption changes,water consumption changes and pathology of organs were observed.In systemic anaphylaxis test,different doses（10μg,100μg,1 000μg）of subunit vaccines（Ag85b-ESAT-6and Hsp65-IL-2were mixed by the ratio of 1：1in quality）were injected subcutaneously to Hartley guinea pigs 3times at the interval of 2days.The body weights changes were observed.Guinea pigs were intravenously injected with the same reagents of double doses in the hind legs after 16 days and allergic reactions were observed.In chronic toxicity test,no clinical symptoms and pathological lesion were observed in mice.In acute toxicity test,the subunit vaccine injection didn＇t cause clinical symptoms,body weights changes,food consumption changes,water consumption changes and pathological lesion in mice.In systemic anaphylaxis test,the subunit vaccine didn＇t cause weights changes.Low dose subunit injection didn＇t cause allergic symptoms in guinea pigs.It suggested that subunit vaccine Ag85b-ESAT-6＋Hsp65-IL-2is safe in mice and guinea pigs,which can be further used in developing prophylactic and treatment vaccines against tuberculosis.

关 键 词：结核分枝杆菌 亚单位疫苗 安全性评价 Ag856-ESAT-6+Hsp65-IL-2 

分 类 号：R378.91[医药卫生—病原生物学]