Prophylactic Vaccines for Schistosomiasis

血吸虫病预防疫苗

• 批准号: 7923601
• 负责人: Donald A Harn
• 金额: $ 31.76万
• 依托单位: UNIVERSITY OF GEORGIA
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7923601
• 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类。血吸虫病数学模型显示，水牛约占中国血吸虫病传播的80%，并预测具有40-45%功效的疫苗将显着减少中国血吸虫病的传播。我们使用 SjCTPI-Hsp70 和 SjC23-Hsp70 质粒 DNA 疫苗结合 IL-12 表达质粒在水牛中进行了两项疫苗功效试验。结果表明，与 pVAX 质粒 DNA 接种的水牛相比，SjC23-Hsp70 和 SjCTPI-Hsp70 疫苗在成虫负荷、肝卵以及重要的是粪便毛虫孵化率方面均能降低 50% 或更高。此修订申请的目标是确定这种高水平疫苗功效需要配方的哪些方面，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，以确认质粒 DNA 构建体中包含 Hsp70 可增强疫苗功效，并确定是否还需要共同施用 IL-12 表达质粒。接下来，我们将确定是否可以通过施用蛋白质抗原加强免疫而不是质粒 DNA 加强免疫来增强疫苗功效，并且我们将与可溶性重组 SJC23 和 SjCTPI 抗原以及与微珠缀合的这些抗原进行比较，以增强抗原呈递细胞激活。然后，我们将确定同时施用两种疫苗的最佳形式是否能在水牛中产生比接种任一单一疫苗的水牛更大的功效。我们相信，拟议的研究将产生一种或多种预防性疫苗，其功效水平高于我们现有的 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 SJC23 和 SjCTPI 疫苗在水牛中的功效是否需要使用 IL-12 或 Hsp70。目标 2. 确定蛋白质抗原增强剂（可溶性​​或微珠缀合物形式）是否会提高 SJC23 或 SjCTPI 疫苗在水牛中的功效？目标 3. 确定在水牛中联合接种优化的 SJC23 和 SjCTPI 疫苗是否比单独接种任一疫苗更有效？