Prophylactic Vaccines for Schistosomiasis

描述（由申请人提供）：血吸虫病仍然是许多发展中国家人和动物的主要寄生虫感染。日本血吸虫病是一种人畜共患的传染病，主要感染布法罗、牛等家畜和人。日本血吸虫病的数学模型表明，中国约80%的血吸虫病传播来源于布法罗，并预测40-45%效力的疫苗将显著减少中国血吸虫病的传播。我们在布法罗中使用SjCTPI-Hsp 70和SjC 23-Hsp 70质粒DNA疫苗与IL-12表达质粒组合进行了两次疫苗效力试验。结果显示，与pVAX质粒DNA接种的布法罗相比，SjC 23-Hsp 70和SjCTPI-Hsp 70疫苗各自诱导50%或更大的成虫负荷、肝卵减少的功效，并且重要的是粪便毛蚴孵化率减少的功效。本修订申请的目的是确定这种高水平疫苗有效性需要制剂的哪些方面，然后修改疫苗制剂和递送，以提高每种疫苗的有效性。因此，将进行疫苗试验以证实在质粒DNA构建体中包含Hsp 70增强疫苗效力，并确定是否还需要共同施用表达IL-12的质粒。我们接下来将确定是否可以通过施用蛋白质抗原加强而不是质粒DNA加强来增强疫苗效力，并且我们将比较用可溶性重组SJC 23和SjCTPI抗原以及与微珠缀合的这些抗原加强以增强抗原呈递细胞活化。然后，我们将确定两种疫苗的最佳形式的联合给药是否在水布法罗中诱导比用任一种疫苗接种的布法罗更大的效力。我们相信，拟议的研究将产生一种或多种预防性疫苗，其有效性水平将高于我们现有的50%水平，这些疫苗将用于中国和东南亚其他地区，以减少血吸虫病的传播。目标1。确定SJC 23和SjCTPI疫苗在布法罗中的效力是否需要使用IL-12或Hsp 70。目标二。确定可溶性或作为微珠缀合物的蛋白抗原加强是否增加SJC 23或SjCTPI疫苗在水布法罗中的效力？目标3：确定优化的SJC 23和SjCTPI疫苗联合接种是否比单独接种任一种疫苗在布法罗中诱导更大的效力？

DESCRIPTION (provided by applicant): Schistosomiasis remains a major parasitic infection of man and animals in numerous developing countries. Schistosoma japonicum is found in southeast Asia and China and is a zoonotic disease, infecting water buffalo, cattle and other livestock as well as man. A mathematical model of schistosomiasis reveals that water buffalo account for approximately 80% of transmission in China and predicts that vaccines with 40-45% efficacy will significantly reduce transmission of schistosomiasis in China. We performed two vaccine efficacy trials in water buffalo using SjCTPI-Hsp70 and SjC23-Hsp70 plasmid DNA vaccines in combination with an IL-12 expressing plasmid. The results show that the SjC23-Hsp70 and SjCTPI-Hsp70 vaccines each induced efficacy of 50% or greater in reductions in adult worm burden, liver eggs and importantly in fecal miracidial hatching rates compared to pVAX plasmid DNA vaccinated buffalo. The goal of this revised application is to determine which aspects of the formulation are required for this high level of vaccine efficacy and then to modify vaccine formulation and delivery to enhance the efficacy of each of these vaccines. Thus vaccine trials will be performed to confirm that the inclusion of Hsp70 in the plasmid DNA constructs enhances vaccine efficacy and determine if co-administration of an IL-12 expressing plasmid is also required. We will next determine if vaccine efficacy can be enhanced by administration of a protein antigen boost instead of a plasmid DNA boost and we will compare boosting with soluble recombinant SJC23 and SjCTPI antigens as well as these antigens conjugated to micro-beads to enhance antigen presenting cell activation. We will then determine if co-administration of the optimal form of both vaccines induces greater efficacy in water buffalo than buffalo vaccinated with either single vaccine. We believe the proposed studies will give rise to one or more prophylactic vaccines with levels of efficacy greater than the 50% level we already have, that will be used in China and other regions of southeast Asia to reduce transmission of schistosomiasis. Aim 1. Determine if SJC23 and SjCTPI vaccine efficacy in water buffalo requires the use of IL-12 or Hsp70. Aim 2. Determine if a protein antigen boost, either soluble or as micro-bead conjugates increase efficacy of SJC23 or SjCTPI vaccines in water buffalo? Aim 3. Determine if vaccination with a combination of the optimized SJC23 and SjCTPI vaccines induce greater efficacy in water buffalo than when either vaccine is administered singly?