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首页> 外文期刊>Infection and immunity >Identification of Potential Vaccine and Drug Target Candidates by Expressed Sequence Tag Analysis and Immunoscreening of Onchocerca volvulus Larval cDNA Libraries
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Identification of Potential Vaccine and Drug Target Candidates by Expressed Sequence Tag Analysis and Immunoscreening of Onchocerca volvulus Larval cDNA Libraries

机译：通过表达的序列标签分析和对盘尾丝虫幼虫cDNA文库的免疫筛选鉴定潜在的疫苗和药物靶标候选物

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The search for appropriate vaccine candidates and drug targets against onchocerciasis has so far been confronted with several limitations due to the unavailability of biological material, appropriate molecular resources, and knowledge of the parasite biology. To identify targets for vaccine or chemotherapy development we have undertaken two approaches. First, cDNA expression libraries were constructed from life cycle stages that are critical for establishment of Onchocerca volvulus infection, the third-stage larvae (L3) and the molting L3. A gene discovery effort was then initiated by random expressed sequence tag analysis of 5,506 cDNA clones. Cluster analyses showed that many of the transcripts were up-regulated and/or stage specific in either one or both of the cDNA libraries when compared to the microfilariae, L2, and both adult stages of the parasite. Homology searches against the GenBank database facilitated the identification of several genes of interest, such as proteinases, proteinase inhibitors, antioxidant or detoxification enzymes, and neurotransmitter receptors, as well as structural and housekeeping genes. Other O. volvulus genes showed homology only to predicted genes from the free-living nematode Caenorhabditis elegans or were entirely novel. Some of the novel proteins contain potential secretory leaders. Secondly, by immunoscreening the molting L3 cDNA library with a pool of human sera from putatively immune individuals, we identified six novel immunogenic proteins that otherwise would not have been identified as potential vaccinogens using the gene discovery effort. This study lays a solid foundation for a better understanding of the biology of O. volvulus as well as for the identification of novel targets for filaricidal agents and/or vaccines against onchocerciasis based on immunological and rational hypothesis-driven research.
机译：由于缺乏生物材料，适当的分子资源以及对寄生虫生物学的了解，迄今为止，寻找合适的候选疫苗和针对小规模盘尾丝虫病的药物靶标面临着一些限制。为了确定疫苗或化学疗法开发的目标，我们采取了两种方法。首先，从生命周期阶段构建cDNA表达文库，这对于建立圆盘螺虫，第三阶段幼虫（L3）和蜕皮L3至关重要。然后通过对5,506个cDNA克隆进行随机表达的序列标签分析来启动基因发现工作。聚类分析表明，与微丝虫，L2和寄生虫的两个成虫阶段相比，在两个或两个cDNA文库中的一个或两个中，许多转录本均被上调和/或阶段特异性。通过GenBank数据库进行同源性搜索，有助于鉴定几个感兴趣的基因，例如蛋白酶，蛋白酶抑制剂，抗氧化剂或排毒酶，神经递质受体以及结构和管家基因。其他食蟹曲霉基因仅与来自自由生活线虫秀丽隐杆线虫的预测基因显示同源性，或者是全新的。一些新型蛋白质含有潜在的分泌前导物。其次，通过用来自假定免疫个体的人血清库对蜕皮的L3 cDNA文库进行免疫筛选，我们鉴定了六种新颖的免疫原性蛋白质，如果使用基因发现方法，这些蛋白质原本不会被鉴定为潜在的疫苗原。这项研究为更好地了解旋毛虫的生物学以及基于免疫学和理性假设驱动的研究确定杀线虫剂和/或抗盘尾丝虫病疫苗的新目标奠定了坚实的基础。

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