SCHISTOSOMIASIS JAPONICA AND PARAGONIMIASIS--GENETIC DIVERSITY AND VACCINES

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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.