Schistosomiasis Vaccine Development and Morbidity throughout the Life Course

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DESCRIPTION (provided by applicant): The present proposal outlines the establishment of a Tropical Medicine Research Center (TMRC) in the Philippines at the Research Institute for Tropical Medicine (RITM) located in Alabang, Muntinlupa City. This program project addresses several aspects of schistosomiasis, one of WHO identified neglected tropical diseases, with the overall goals of examining the impact of protective and maladaptive immune responses to Schistosoma japonicum on human infection and disease throughout the life course. The program will have 3 projects, each are linked to the national control schistosomiasis control program in order that insights gained through this TMRC will have an immediate impact on the control of schistosomiasis . The 3 projects are: Project 1 will evaluate the impact of buffalo vaccination with rSj97 on buffalo and human infection. Project 2, will examine the impact of maternal PZQ treatment on the longevity of in utero immune sensitization and schistosome-related morbidity in early childhood. Project 3 will examine the interactions among maternal PZQ treatment, dysregulated collagen metabolism, and birth outcomes in maternal-child dyads from our ongoing RCT. In addition to the 3 projects, this TMRC will expand the research capacity of RITM through the establishment of an Administrative Core, Immunology Multiplex Core and Data Management Core in collaboration with the Center for International Health Research at Rhode Island Hospital (CIHR-RIH) in the US. RELEVANCE: This program will provide strong data in support of an FDA IND for the Sj97 vaccine, inform risk-benefit analysis with respect to targeting women for treatment with Praziquantel during pregnancy, and highlight mechanisms of dysregulated collagen metabolism in mediating poor pregnancy outcomes among Schistosoma japonicum-infected women. Project 1: Schistosomiasis Vaccine Development Project Leader (PL): Jiz, M. (Description as provided by applicant): The overall aim of this Project 1 is to accelerate the development of recombinant paramyosin as a vaccine against schistosomiasis japonica. Schistosomiasis, caused by three principle species of dioecious trematodes (flatworms), currently infects over 250 million individuals, results in 1.53 million DALYs lost per annum, and contributes to poor health and economic stagnation in endemic areas. Although schistosomiasis is effectively treated with praziquantel (PZQ), rapid re-infection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. We will evaluate the efficacy and safety of paramyosin (rSj97), the target of protective Th2 and IgE responses in our human studies, in vaccine trials in water buffalo, a major bovine reservoir of schistosomiasis. We will explore a range of vaccine adjuvants in field-based challenge experiments in water buffalos. We will conclude with a large scale, community based vaccine trial in buffalo designed to test the hypothesis that effective vaccination of water buffalo will reduce the transmission of schistosomiasis japonica to humans. The outcome of these studies will be an optimized, adjuvanted, paramyosin-based vaccine for bovine schistosomiasis japonica with preclinical data on safety and efficacy in a large animal model. RELEVANCE: Vaccine development for schistosomiasis remains a promising avenue to better control this chronic and debilitating disease. This TMRC project will provide a strong basis to deploy a bovine vaccine and will support an FDA IND application for follow-on Phase l/ll clinical trials to develop a human vaccine that limits re-infection and consequent morbidity and mortality.