Pokharel Daya Ram, Rai Reeta, Nandakumar Kodumudi Krithika, Reddy Maryada Venkata Rami, Rathaur Sushma
Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi-221005, UP, India.
Vaccine. 2006 Sep 11;24(37-39):6208-15. doi: 10.1016/j.vaccine.2006.05.103. Epub 2006 Jun 15.
A zinc containing metalloprotease, 175 kDa collagenase, purified from adult female Setaria cervi showed strong cross-reactivity with sera from putatively immune (PI) individuals (unpublished observation) and induced cytotoxicity to B. malayi L3 larvae and microfilariae by ADCC mechanism [Srivastava Y, Bhandari YP, Reddy MVR, Harinath BC, Rathaur S. An adult 175 kDa collagenase antigen of Setaria cervi in immunoprophylaxis against Brugia malayi. J Helminth 2004;78:347-52]. These preliminary observations suggested the immunoprotective nature of collagenase. To confirm the vaccine potential of this protease, a vaccine trial was conducted in jirds (Meriones unguiculatus) against human filarial parasite B. malayi. The vaccination resulted into a mean protection level of 75.86% and produced high level of protease neutralizing antibodies. Cytokine analysis in immune jirds sera suggested a mixed Th1/Th2 type cellular immune response whereas ELISA, immunoblotting and enzyme antibody inhibition assay revealed the presence of specific anti-collagenase antibodies. Taken together, all these results suggest that S. cervi 175 kDa collagenase could form the basis of an effective molecular vaccine against human lymphatic filariasis.
从成年雌性鹿丝状线虫中纯化得到的一种含锌金属蛋白酶——175 kDa胶原酶,与假定免疫(PI)个体的血清显示出强烈的交叉反应性(未发表的观察结果),并通过抗体依赖的细胞介导的细胞毒性(ADCC)机制对马来布鲁线虫L3幼虫和微丝蚴产生细胞毒性[Srivastava Y, Bhandari YP, Reddy MVR, Harinath BC, Rathaur S. 鹿丝状线虫的一种成年175 kDa胶原酶抗原在抗马来布鲁线虫免疫预防中的作用。《寄生虫学杂志》2004年;78:347 - 52]。这些初步观察结果表明了胶原酶的免疫保护性质。为了证实这种蛋白酶的疫苗潜力,在沙鼠(长爪沙鼠)中针对人类丝虫寄生虫马来布鲁线虫进行了疫苗试验。接种疫苗产生了平均75.86%的保护水平,并产生了高水平的蛋白酶中和抗体。对免疫沙鼠血清进行的细胞因子分析表明存在混合的Th1/Th2型细胞免疫反应,而酶联免疫吸附测定(ELISA)、免疫印迹和酶抗体抑制试验显示存在特异性抗胶原酶抗体。综上所述,所有这些结果表明,鹿丝状线虫175 kDa胶原酶可成为一种有效的抗人类淋巴丝虫病分子疫苗的基础。