Adjuvant and Dose Optimization of Paramyosin based Vaccines for Schistosmiasis

描述（由申请方提供）：本次R21再提交的总体目的是优化和检测基于副肌球蛋白的牛日本血吸虫病疫苗的有效性。这种疫苗的目的是减少动物疾病和减少血吸虫病传播给人类。由雌雄异株吸虫（扁形虫）的三种主要物种引起的血吸虫病目前感染了超过2.5亿人，估计导致2-15%的慢性残疾，并导致流行地区的健康状况不佳和经济停滞。虽然血吸虫病是有效的治疗吡喹酮（PZQ），快速再感染与反弹的发病率排除了有效的控制基础上单独化疗，并证明目前的努力，为这些寄生虫的疫苗开发。在感染人类的寄生虫中，S.日本血吸虫的独特之处在于具有促成人类传播的重要动物宿主，并且最近的两项研究已经证明，在流行地区，药物治疗或消灭水牛可以将血吸虫的传播显著减少75%至93%。japonicum对人类在我们最近的试点实验中，与单独使用佐剂处理的布法罗相比，用Montanide伊萨206中的重组全长副肌球蛋白接种布法罗导致尾蚴攻击后的中值蠕虫负担减少52%。我们建议通过在水牛（一种大型血吸虫病动物模型）中进行安全性和有效性试验来加速副肌球蛋白作为人血吸虫病和牛血吸虫病疫苗的开发。成功的牛疫苗将：1）具有直接的兽医应用，2）直接减少对人类的传播，以及3）作为非啮齿动物大型动物模型，支持FDA IND申请，以启动基于副肌球蛋白的疫苗在人类中的I/II期试验。 公共卫生相关性：本次R21再提交的总体目标是优化和检测基于副肌球蛋白的牛日本血吸虫病疫苗的有效性。这种疫苗的目的是减少动物疾病和减少血吸虫病传播给人类。由雌雄异株吸虫（扁形虫）的三种主要物种引起的血吸虫病目前感染了超过2.5亿人，估计导致2-15%的慢性残疾，并导致流行地区的健康状况不佳和经济停滞。虽然血吸虫病是有效的治疗吡喹酮（PZQ），快速再感染与反弹的发病率排除了有效的控制基础上单独化疗，并证明目前的努力，为这些寄生虫的疫苗开发。

DESCRIPTION (provided by applicant): The overall aim of this R21 resubmission is to optimize and test the efficacy of a paramyosin based vaccine against bovine schistosomiasis japonica. The goal of this vaccine is to reduce animal disease and reduce transmission of schistosomiasis to humans. Schistosomiasis, caused by three principle species of dioecious trematodes (flatworms), currently infects over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas. Although schistosomiasis is effectively treated with Praziquantel (PZQ), rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Amongst the species of schistosomes that infect humans, S. japonicum is unique in having significant animal reservoirs that contribute to human transmission and two recent studies have demonstrated that drug curing or eliminating water buffalos in endemic areas can profoundly reduce, by 75 to 93%, transmission of S. japonicum to humans. In our recent pilot experiments, vaccination of water buffalo with recombinant, full length paramyosin in Montanide ISA 206 resulted in 52% reduction in median worm burden after cercarial challenge compared to buffalo treated with adjuvant alone. We propose to accelerate the development of paramyosin as a vaccine for both human and bovine schistosomiasis by conducting safety and efficacy trials in water buffaloes, a large animal model of schistosomiasis. A successful bovine vaccine would: 1) have direct veterinary application, 2) directly reduce transmission to humans, and 3) serve as a non-rodent large animal model supporting an FDA IND application to initiate Phase I/II trials of a paramyosin based vaccine in humans. PUBLIC HEALTH RELEVANCE: The overall aim of this R21 resubmission is to optimize and test the efficacy of a paramyosin based vaccine against bovine schistosomiasis japonica. The goal of this vaccine is to reduce animal disease and reduce transmission of schistosomiasis to humans. Schistosomiasis, caused by three principle species of dioecious trematodes (flatworms), currently infects over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas. Although schistosomiasis is effectively treated with Praziquantel (PZQ), rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites.