SCHISTOSOMIASIS JAPONICA AND PARAGONIMIASIS--GENETIC DIVERSITY AND VACCINES

日本血吸虫病和肺吸虫病——遗传多样性和疫苗

• 批准号: 6201283
• 负责人: SHU-XIAN LIU
• 金额: $ 16.25万
• 依托单位: NATIONAL INSTITUTE OF PARASITIC DISEASES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6201283
• 关键词: China; Primates; Schistosoma japonicum; Trematoda; Ungulate; animal population study; cysteine endopeptidases; disease vectors; dogs; gene therapy; genetic polymorphism; genetic strain; glutathione transferase; hamsters; helminthiasis; laboratory mouse; laboratory rat; recombinant DNA; restriction fragment length polymorphism; species difference; synthetic vaccines; systematic biology

Trematode infections with either the Schistosoma japonicum complex or paragonimus spp. are among the most important public health threats in the highly populated rural areas of the Yangtze River Basin of China. We propose to apply modern and innovative biotechnology towards the study and control of these two trematodiases. For S. japonicum we propose to develop two types of molecular vaccines using either recombinant polypeptides or plasmid (naked) DNA. A number of candidate cDNAs and/or their expressed polypeptides will be examined including a particularly promising S. japonicum glutathione-S-transferase (GST). In experimental animal models with mice, pigs and water buffaloes we have found that recombinant GST functions as an effective anti-disease vaccine for schistosomiasis japonica; because water buffalo are important animal reservoirs for this infection in humans we will evaluate GST and other vaccine candidates for their ability to interrupt transmission by reservoir host immunization. The second part of the S. japonicum project will rely on collecting molecular genetic data, which is specific for localized geographic Chinese strains. Using RAPD, rRNA gene RFLP, and single gene copy sequence methodologies we propose to uncover infraspecific genetic diversity (or cryptic species) with S. japonicum populations prevalent in the Yangtze River Basin. We will look for the emergence or reemergence of new Chinese schistosome species and determine the impact of sequence diversity on recombinant vaccine development. Approaches to paragonimiasis will follow similar lines (molecular vaccines and genetic diversity), but because of a paucity of existing taxonomic information we will first establish a sound taxonomic framework for the genus paragonimus in China with emphasis in this proposal on P westermani hypothesized species complex and the hypothesized p. skrjabini species complex. The molecular diversity data will be used to evaluate molecular vaccine candidates for paragonimiasis including a GST and cysteinyl protease.

日本血吸虫复合体或 并殖吸虫属是世界上最重要的公共卫生威胁之一， 中国长江流域人口稠密的农村地区。我们 建议将现代和创新的生物技术应用于研究， 控制这两种吸虫病。对于鼠伤寒沙门氏我们建议开发japonicum 两种类型的分子疫苗使用重组多肽或 质粒（裸）DNA。许多候选cDNA和/或它们的表达 将检查多肽，包括特别有前途的S. 大豆谷胱甘肽-S-转移酶（GST）。在实验动物模型中 用小鼠、猪和水牛，我们发现重组GST 作为血吸虫病的有效抗病疫苗 日本;因为水布法罗是重要的动物水库， 我们将评估GST和其他候选疫苗， 它们通过宿主免疫阻断传播的能力。 第二部分是S. japonicum项目将依靠收集 分子遗传学数据，这是特定的地方地理中国 菌株 采用RAPD、rRNA基因RFLP、单基因拷贝测序等方法 我们提出的揭示种下遗传多样性的方法（或 隐种）与S.长江流行的日本血吸虫种群 河流域我们将寻找新中国的出现或重新出现 确定序列多样性的影响， 重组疫苗开发。以下将介绍如何进行平行免疫 类似的品系（分子疫苗和遗传多样性），但由于 缺乏现有的分类信息，我们将首先建立一个 中国并殖吸虫属的合理分类框架 在这一建议对P westermani假设种复合体和 假设的斯氏狸殖吸虫物种复合体分子多样性数据 将用于评估并殖吸虫的分子疫苗候选物 包括GST和半胱氨酰蛋白酶。