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用鹿丝状线虫175 kDa胶原酶进行疫苗接种可使沙鼠对马来布鲁线虫感染产生高水平的保护作用。

Vaccination with Setaria cervi 175 kDa collagenase induces high level of protection against Brugia malayi infection in jirds.

作者信息

Pokharel Daya Ram, Rai Reeta, Nandakumar Kodumudi Krithika, Reddy Maryada Venkata Rami, Rathaur Sushma

机构信息

Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi-221005, UP, India.

出版信息

Vaccine. 2006 Sep 11;24(37-39):6208-15. doi: 10.1016/j.vaccine.2006.05.103. Epub 2006 Jun 15.

Abstract

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from adult female Setaria cervi showed strong cross-reactivity with sera from putatively immune (PI) individuals (unpublished observation) and induced cytotoxicity to B. malayi L3 larvae and microfilariae by ADCC mechanism [Srivastava Y, Bhandari YP, Reddy MVR, Harinath BC, Rathaur S.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.

摘要

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。

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