SCHISTOSOMIASIS JAPONICA AND PARAGONIMIASIS--GENETIC DIVERSITY AND VACCINES

吸虫感染日本血吸虫复合体或 并殖吸虫。是世界上最重要的公共卫生威胁之一 中国是长江流域人口稠密的农村人。我们 建议将现代和创新的生物技术应用于研究和 控制这两种吸虫酶。对于日本血吸虫，我们建议开发 使用重组多肽和重组多肽的两种分子疫苗 质粒(裸)DNA。一些候选的cDNA和/或其表达 多肽将被检测，其中包括一种特别有希望的S. 谷胱甘肽-S-转移酶(GST)。在实验动物模型中 在小鼠、猪和水牛身上，我们发现重组GST 作为血吸虫病的有效抗病疫苗 日本；因为水牛是重要的动物蓄水池 我们将评估GST和其他候选疫苗对人类的感染 它们通过宿主免疫阻断传播的能力。 日本血吸虫项目的第二部分将依靠收集 分子遗传学数据，专用于地方性中国人 菌株。利用随机扩增多态性DNA、rRNA基因RFLP和单基因拷贝序列 我们提出的揭示种下遗传多样性的方法(或 神秘物种)，日本血吸虫种群在长江中盛行 江河流域。我们将期待新中国人的出现或重新崛起 并确定序列多样性对血吸虫物种的影响 重组疫苗的开发。治疗并殖吸虫病的方法将随之而来 相似的品系(分子疫苗和遗传多样性)，但因为 现有分类学信息的匮乏，我们将首先建立一个 中国并殖吸虫属合理的分类框架及重点 在这项关于P-westermani假想物种复合体和 假想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病的分子疫苗候选 包括GST和半胱氨酸蛋白酶。

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.