Prophylactic Vaccines for Schistosomiasis

血吸虫病预防疫苗

• 批准号: 7591665
• 负责人: Donald A Harn
• 金额: $ 11.6万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2009-04-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7591665
• 关键词: Accounting; Adult; Animals; Antibody Formation; Antigen-Presenting Cells; Antigens; Buffaloes; Cattle; Child; China; Combined Vaccines; DNA Vaccines; Developed Countries; Developing Countries; Disease; Drug Formulations; Enzymes; Family suidae; Goals; Growth; HIV; Health; Immune response; Infection; Integral Membrane Protein; Interleukin-12; Liver; Livestock; Measures; Monoclonal Antibodies; Mus; Output; Parasitic infection; Phagocytosis; Pharmaceutical Preparations; Plasmids; Proteins; Public Health; Recombinant Proteins; Recombinants; Schistosoma; Schistosoma japonicum; Schistosomiasis; Sheep; Southeastern Asia; Treatment Protocols; Triose-Phosphate Isomerase; Tuberculosis; Vaccinated; Vaccination; Vaccines; Water Buffalo; antigen processing; cytokine; disease transmission; efficacy trial; egg; hatching; improved; man; mathematical model; pathogen; plasmid DNA; prophylactic; research study; response; transmission process; vaccine efficacy

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?

描述（由申请人提供）：血吸虫病仍然是许多发展中国家人类和动物的主要寄生虫感染。 Japonicum血吸虫可在东南亚和中国发现，是一种人畜共患病，感染水牛，牛和其他牲畜以及人类。血吸虫病的数学模型表明，水牛大约占中国传播的80％，并预测，疗效40-45％的疫苗将显着降低中国血吸虫病的传播。我们使用SJCTPI-HSP70和SJC23-HSP70质粒DNA疫苗与IL-12表达质粒一起，在水牛油水牛中进行了两项疫苗功效试验。结果表明，SJC23-HSP70和SJCTPI-HSP70疫苗各感诱导的疗效在成年蠕虫负担，肝卵中的减少降低50％或更高，并且与PVAX质粒DNA疫苗接种的Buffalo相比，成人蠕虫负担，肝卵的降低以及重要的是粪便奇迹型孵化率。该修订后的应用的目的是确定该高水平疫苗功效所需的配方的哪个方面，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，以确认将Hsp70纳入质粒DNA构建体中会增强疫苗功效，并确定是否还需要对表达质粒的IL-12的共同给药。接下来，我们将通过给药而不是质粒DNA提升来确定疫苗功效是否可以提高疫苗功效，我们将与可溶性重组SJC23和SJCTPI抗原以及这些抗原以及这些抗原相结合的微蛋白相结合，以增强抗原抗原抗原抗原抗原抗原，以增强抗抗原的细胞活化。然后，我们将确定两种疫苗的最佳形式的共同给药是否诱导水牛的疗效比用两种疫苗接种接种的水牛。我们认为，拟议的研究将产生一种或多种预防性疫苗，其功效水平大于我们已经拥有的50％水平，该水平将在中国和东南亚其他地区使用，以减少血吸虫病的传播。 AIM 1。确定水牛的SJC23和SJCTPI疫苗功效是否需要使用IL-12或HSP70。 AIM 2。确定蛋白抗原是可溶性还是微珠偶联物提高SJC23或SJCTPI疫苗在水液水中的疗效？ AIM 3。确定与优化的SJC23和SJCTPI疫苗组合结合的疫苗是否会诱导水牛的疗效，而不是单独施用任何一种疫苗？