三种免疫调节剂增强弓形虫重组ROP2疫苗保护效应的研究  

Three adjuvant formulations on the induced protection of mice immunized with recombinant ROP2 of Toxoplasma gondii

作　　者：陈兴智[1,2] 杨小迪[1] 杨雯[1] 陈勇[1] 刘丽丽[2] 沈继龙[2] 孙新[1] 

机构地区：[1]蚌埠医学院病原生物学教研室,安徽省感染与免疫重点实验室,蚌埠233030 [2]安徽病原生物学省级实验室,人兽共患病安徽省重点实验室,安徽医科大学病原生物学教研室,合肥230032

出　　处：《中国人兽共患病学报》2013年第6期570-574,共5页Chinese Journal of Zoonoses

基　　金：国家重点基础研究发展规划项目(973计划)(No.2010CB530001);安徽省教育厅重点资助项目(No.KJ2012A201)~~

摘　　要：目的观察弗氏佐剂(Freund’s Adjuvant,FA)、匹多莫德(Pidotimod,PT)和西咪替丁(Cimetidine,CIM)等3种免疫调节剂增强重组弓形虫棒状体蛋白2(rROP2)疫苗的免疫保护效应。方法将100只BALB/c小鼠随机分为PBS对照组、重组rROP2疫苗组、FA-rROP2疫苗组、PT-rROP2疫苗组和CIM-rROP2疫苗组等5组;FA、PT和CIM分别与rROP2抗原混合皮下注射免疫,检测小鼠细胞免疫和体液免疫指标,并观察弓形虫RH株攻击感染后的生存时间。结果 FA-rROP2组、CIM-rROP2组小鼠血清IFN-γ、特异性IgG、脾细胞增殖活性及外周血CD4+/CD8+比值均显著高于rROP2蛋白组(P<0.05);PT对外周血CD4+/CD8+比值无明显影响,但显著增加了IFN-γ的水平及脾细胞增殖活性。小鼠攻击试验表明,FA-rROP2组、PT-rROP2组以及CIM-rROP2组小鼠存活时间显著长于rROP2组和PBS对照组组;rROP2蛋白组各项指标均显著高于PBS组(P<0.05)。结论 FA、PT和CIM可增强rROP2蛋白抗原诱导的细胞免疫和体液免疫反应,都能延长攻击感染小鼠的生存时间,具有增强rROP2蛋白疫苗保护效应的功能。其中CIM的佐剂样免疫促进作用接近于FA,但副作用显著低于后者,具有临床实用的潜在价值。The aim was to observe the effect of 3 formulations of immuno-modulators on immune response and protective efficacy induced by rROP2 of Toxoplasma gondii in mice. A total of 100 BALB/c mice were randomly divided into 5 groups： PBS, rROP2, rROP2-Freund adjuvant （FA）, rROP2 pidotimod （PT）, and rROP2-cimetidine （CIM）. The mice were vaccinat ed subcutaneously 3 times in 2-week intervals. The parameters in humoral and cellular immune response were detected. The survival time of mice was evaluated after T. gondii RH tachyzoites challenge. The results clearly showed that FA and CIM sig nificantly increased the expression of IFN-7 and IgG, CD4＋/CD8＋ ratio, and proliferation of splenocytes （P〈0.05） than PBS and rROP2 groups. PT, however, has no significant influence on the CD4＋/CD8＋ ratio but significantly increased the level of IFN-7 and proliferation of splenocytes （P〈0.05）. After challenged with virulence strain of RH tachyzoites, mice vaccinated with ROP2/CIM, rROP2 /PT and rROP2/FA survived longer than the control and rROP2 groups （P〈0.05）. Even mice vac cinated with rROP2 alone gave rise to a significant immune protection against tachyzoites challenging （P〉0.05）. Three of the immuno-modulators, FA, PT, and CIM, could individually enhance the protective immunity against T. gondii infection induced by rROP2 candidates. Taken into consideration of the efficacy and by side effects, cimetidine has promising po tential in clinic practice of ToxopLasma vaccine development.duced by rROP2 candidates. Taken into consideration of the efficacy and by side effects, cimetidine has promising po tential in clinic practice of ToxopLasma vaccine develop- ment.

关 键 词：弓形虫 弗氏佐剂 匹多莫德 西咪替丁 ROP2蛋白 免疫佐剂 

分 类 号：R382.5[医药卫生—医学寄生虫学]