Prophylactic Vaccines for Schistosomiasis

描述（由申请人提供）：在许多发展中国家，血吸虫病仍然是人类和动物的主要寄生虫感染。日本血吸虫发现于东南亚和中国，是一种人畜共患疾病，感染水牛、牛和其他牲畜以及人。一个血吸虫病的数学模型显示，水牛约占中国血吸虫病传播的80%，并预测40-45%效力的疫苗将显著减少中国血吸虫病的传播。我们将SjCTPI-Hsp70和sjj23 - hsp70质粒DNA疫苗与IL-12表达质粒联合在水牛身上进行了两项疫苗效力试验。结果表明，与接种pVAX质粒DNA的水牛相比，sjj23 - hsp70和SjCTPI-Hsp70疫苗在减少成虫负担、肝脏卵和重要的粪便微生物孵化率方面的效果均达到50%或以上。这项修订申请的目标是确定配方的哪些方面需要这种高水平的疫苗功效，然后修改疫苗配方和递送，以增强每种疫苗的功效。因此，将进行疫苗试验，以确认在质粒DNA结构中包含Hsp70可增强疫苗效力，并确定是否还需要同时施用表达IL-12的质粒。接下来，我们将确定是否可以通过蛋白质抗原增强剂而不是质粒DNA增强剂来增强疫苗的效力，并将增强剂与可溶性重组SJC23和SjCTPI抗原以及这些抗原结合到微球上以增强抗原提呈细胞的激活进行比较。然后，我们将确定两种疫苗的最佳形式共同施用是否比接种任何单一疫苗的水牛产生更大的效力。我们相信，拟议的研究将产生一种或多种预防疫苗，其效力水平高于我们现有的50%水平，这些疫苗将在中国和东南亚其他地区用于减少血吸虫病的传播。目的1。确定sjj23和SjCTPI疫苗在水牛中的有效性是否需要使用IL-12或Hsp70。目标2。确定可溶性或微球偶联蛋白抗原增强剂是否能提高水牛SJC23或SjCTPI疫苗的效力？目标3。确定与优化的SJC23和SjCTPI疫苗联合接种是否比单独接种任一疫苗对水牛产生更大的效力？

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?