Flagellar antigens of Trichomonas vaginalis

描述（由申请人提供）：在所有性传播疾病中，滴虫病是最常见的非病毒感染。据估计，全世界每年有2亿人感染，仅在美国每年就有400多万新病例。该疾病的病原体，阴道毛滴虫，是一种原生动物寄生虫，有四个前鞭毛和一个复发鞭毛。最近，滴虫病与严重的并发症有关，如宫颈癌的发展、感染人类免疫缺陷病毒的高概率和不良妊娠结局。尽管毛滴虫病发病率高，并发症多，但其致病机制尚不清楚，一些耐药的毛滴虫株已被发现。流浪汉正在出现。因此，迫切需要在寄生虫的亚细胞结构领域进行研究;（a）粘附分子，其抗血清将具有预防价值（B）发现抗寄生虫药物的新靶点（c）更好地理解寄生虫的亚细胞结构（免疫生物学和功能）。我们的初步研究揭示了几种鞭毛多肽，在免疫印迹中显示出与人抗毛滴虫病血清的强免疫反应性。此外，来自不同实验室的研究表明，T。迷走神经细胞在人类和实验动物中具有免疫原性。基于这些报道和我们的初步研究，我们推测寄生虫的鞭毛蛋白参与寄生虫对宿主细胞的粘附。将通过分离鞭毛，然后进行免疫沉淀和在十二烷基硫酸钠聚丙烯酰胺凝胶电泳（SOSPAGE）上分析鞭毛抗原来检验这一假设。鞭毛抗原将用于免疫兔，兔抗血清将用于筛选寄生虫的粘附抑制。其抗血清显示显著程度的粘附抑制的鞭毛抗原将被认为是鞭毛粘附素。粘附素作为配体在寄生虫与宿主细胞的细胞粘附中的作用将通过粘附/粘附抑制测定法进行大量检查。将对粘附素进行表征，以了解它们是否暴露于表面以及反应表位的生物化学组成。预计这些研究结果将为鞭毛蛋白在T.阴道炎

DESCRIPTION (provided by the applicant): Of all the sexually transmitted diseases, Trichomoniasis is the most common non-viral infection. An estimated 200 million people are infected annually all over the world, with greater than four million new cases per year in the United States alone. The agent of the disease, Trichomonas vaginalis, is a protozoan parasite with four anterior flagella and a recurrent flagellum. Trichomoniasis has recently been associated with severe complications such as development of cervical cancer, high probability of infection by human immunodeficiency virus and adverse pregnancy outcomes. In spite of the high incidence of trichomoniasis and the complications associated with the disease, the mechanisms of pathogenesis of the parasite are not well understood and some drug resistant strains of T. vaginalis are emerging. Therefore, there is urgent need for research in the area of subcellular structures of the parasite for; (a) adhesion molecules whose antisera will be of prophylactic value (b) discovery of new targets for anti-parasitic drugs (c) better understanding (immunobiology and functions) of the subcellular structures of the parasite. Our Preliminary Studies revealed several flagellar polypeptides that showed strong immuno-reactivity with human anti-Trichomoniasis sera in immunoblots. Furthermore, studies from different laboratories have shown that T. vaginalis cells are immunogenic in humans and laboratory animals. Based on these reports and our Preliminary Studies we hypothesize that flagellar proteins of the parasite are involved in adhesion of the parasite to the host cells. This hypothesis will be tested by isolating flagella followed by immunoprecipitation and analysis of flagellar antigens on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SOSPAGE). The flagellar antigens will be used to immunize rabbits and the rabbit antisera will be utilized to screen the parasite for adhesion inhibition. Flagellar antigens whose antisera show significant degree of adhesion inhibition will be considered to be flagellar adhesins. The role of the adhesins as ligands in the cytoadhesion of the parasite to host cells will be tufty examined by adhesion/adhesion inhibition assays. The adhesins will be characterized to know if they are surface exposed and the biochemical make up of the reacting epitopes. It is anticipated that the results of these studies will yield new information about the roles of flagellar proteins in the pathogenesis of T. vaginatis.