Analysis of schistosomicidal component(s) within mouse serum and its implications for novel drug development

血吸虫病是一种由血吸虫引起的寄生虫病，仍然是最重要的被忽视的热带病（NTD），尽管目前的大规模消除计划依赖于单一药物（吡喹酮）的有效性。由于2.5亿多人主要在热带和亚热带地区受到感染，高再感染率和新出现的耐药性迫切需要新的治疗方法。已建立的小鼠感染模型已成功地用于不同研究小组对疾病的免疫生物学的研究。然而，有趣的是，大部分穿透性尾蚴（>80%）在小鼠中不会发育成蠕虫，尽管原因尚不清楚。因此，使用这种模型来测试新的疫苗或驱虫药目前受到质疑。对我们新开发的无细胞体外培养系统进行的初步研究表明，分级小鼠血清可以快速有效地杀死人体内寄生虫的几乎所有生命周期阶段。因此，本项目旨在鉴定这些可溶性的宿主特异性分子及其作用模式。将实施蛋白质组学、生物化学和生物技术等研究平台，以开发针对这种使人衰弱的血管寄生虫感染的新的治疗干预措施。

Schistosomiasis, a parasitic disease caused by a blood-dwelling fluke, remains the most important neglected tropical disease (NTD) despite large elimination programs that currently depend on the effectiveness of a single drug (Praziquantel). With more than 250 million people infected primarily in tropical and subtropical areas, high reinfection rates and emerging drug resistance urgently require new treatment approaches. The well-established murine infection model has beensuccessfully used in different research groups for the investigation of the immunobiology of the disease. Interestingly, however, a large proportion of penetrating cercariae (>80%) does not develop into adult worms in mice, although the cause is still unclear. Therefore, the use of this model for testing new vaccines or anthelminthics is currently being questioned. Preliminary investigations in our newly developed, cell-free in vitro culture system for generation of Schistosoma mansoni developmental stages up to juvenile worms have shown that fractionated mouse serum rapidly and efficiently kills almost all life cycle stages of the parasite that occur in humans. Thus, the present project aims at identifying these soluble, host-specific molecules and their mode of action. Research platforms such as proteomics, biochemistry and biotechnology will be implemented to develop new therapeutic interventions against this debilitating vascular parasitic infection.