结核分枝杆菌Ag85A和Ag85B重组蛋白疫苗联合佐剂的治疗作用

Therapeutic effects of Ag85A and Ag85B recombinat protein vaccines from Mycobacterium tuberculosis combined with adjuvant

目的 研究结核分枝杆菌Ag85A和Ag85B重组蛋白疫苗联合佐剂对结核的治疗作用.方法 用结核分枝杆菌H37Rv通过尾静脉注射60只BALB/c小鼠,分别用生理盐水、利福平、草分枝杆菌F.U.36注射液、佐剂77-1、Ag85A和Ag85B重组蛋白疫苗、Ag85A和Ag85B重组蛋白疫苗联合佐剂治疗.免疫结束后2周杀鼠,观察肺和脾病理改变,称取重量,做菌落计数.结果 肺组织病理显示：生理盐水组肺组织病变严重、广泛,佐剂组比生理盐水组病变略轻,病变仍较重、广泛,草分枝杆菌F.U.36注射液组、Ag85A和Ag85B重组蛋白疫苗组、Ag85A和Ag85B重组蛋白疫苗联合佐剂组肺组织病变减轻、局限,3/5区域肺泡结构完整、清晰,利福平组肺组织无病变.与生理盐水组比较,利福平组、草分枝杆菌F.U.36注射液组、Ag85A和Ag85B重组蛋白疫苗联合佐剂组肺脏菌落数分别减少2.11 log、0.76 log和0.57 log;肝脏菌落数分别减少2.11 log、0.74 log和0.44 log（t＞3.21,P＜0.01）.结论 Ag85A和Ag85B重组蛋白疫苗联合佐剂对小鼠结核病具有较好的治疗效果,与草分枝杆菌F.U.36注射液相当.

Objective To evaluate the therapeutic effects of Ag85A and Ag85B recombination protein vaccines combined with adjuvant in mouse model of Mycobacterium tuberculosis infection to establish new immunotherapeutic agents to treat tuberculosis.Methods 60 female BALB/c mice were infected intravenously via the tail vein with Mycobacterium tuberculosis H37RV,then randomly divided into six groups based and treated as follow at the third day after infection：saline,rifampin,Mycobacterium Phlei F.U.36 injection,adjuvant,Ag85A and Ag85B recombinat protein vaccines,Ag85A and Ag85B recombinat protein vaccines combined with adjuvant.Vaccines were injected intramuscularly three times at two-week intervals.Mice were sacrificed two weeks after the final immunization.The lungs and spleens from the mice were taken and their pathological changes,weight and number of mycobacterial colony were examined.Results The histopathological changes of lung showed that the lung lesions were severe and extensive in saline and adjuvant group,the lung lesions were slight and limited,there were relatively clearand normal structure of alveoli in Mycobacterium Phlei F.U.36 injection,adjuvant,Ag85A and Ag85B recombinatprotein vaccines,Ag85A and Ag85B recombinat protein vaccines combined with adjuvant group,there were no lung lesions in rifampin group.Compared with saline group,pulmonary bacterial loads of rifampin group,Mycobacterium Phlei F.U.36 injection group,Ag85A and Ag85B recombinat protein vaccines combined with adjuvant group reduced by 2.11 log,0.76 log,and 0.57 log,liver bacterial loads by 2.11 log,0.74 log,and 0.44 log （t 〉 3.21,P 〈 0.01）,respectively.Conclusions The immunotherapeutic effect of Ag85A and Ag85B recombinat protein vaccines combined with adjuvant is significant in the mouse model of tuberculosis,as that as Mycobacterium Phlei F.U.36 injection.