Development of in vitro assays to determine vaccine efficacy in fish

开发体外测定法以确定疫苗对鱼类的功效

• 批准号: G1000100/1
• 负责人: Chris Secombes
• 金额: $ 19.98万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000100%2F1
• 关键词: Development; vitro; assays; determine; vaccine

Fish farming in the UK has increased dramatically over the last two decades. Scotland currently produces over 130,000 tonnes of Atlantic salmon and is the third largest producer of farmed salmon globally. Around 16,000 tonnes of rainbow trout are also produced in the UK annually. Consumer consumption of farmed fish has trebled in the last ten years, with 1 million salmon meals now eaten each day in the UK. Of various factors that impact on the sustainability of the industry, fish health is key with a number of disease issues of particular concern. To obtain a sustainable aquaculture industry health management is thus necessary and at the heart of this management is the development of new vaccines, which require thorough testing before they can be marketed. This involves large numbers of fish exposed to disease agents, where mortality is used as the end point to test vaccine efficacy. The development of a method that would allow researchers to establish vaccine efficacy more humanely, would significantly reduce the suffering of fish in these trials. Protection by vaccination relies on the production of specific antibodies and the activation of T cells that mediate specific cell-mediated responses, capable of killing infected host cells and activating non-specific defences. The study of these cellular responses is key to reducing the suffering of fish during vaccine trials. Some T cells (T-helper cells) release mediators called cytokines that initiate and regulate the host responses. Different responses can be generated dependent upon the cytokines released. The measurement of these molecules after vaccination can be correlated with the protection conferred by immunisation, a well established method used with reasonable success in mammals.In this study we will determine the numbers of cells producing two cytokines (IL-17 and IL-22) in trout, following vaccination against one of two bacterial pathogens (Yersinia ruckeri or Aeromonas salmonicida) and exposure to the homologous or heterologous pathogen. IL-17 and IL-22 were chosen as they are associated with T-helper cell subpopulations responsible for protection against these types of pathogens in mammals. Their production will be assessed as an in vitro correlate of protection, and the results will serve more generally as a proof of principle for fish, with a view to develop a means to undertake a great deal of vaccine optimisation without the need for lethal challenge experiments. In this way this work will help to reduce fish suffering in future vaccine development studies.

在过去的二十年中，英国的养鱼急剧增加。苏格兰目前生产超过130,000吨的大西洋鲑鱼，是全球养殖鲑鱼的第三大生产商。每年在英国也生产约16,000吨彩虹鳟鱼。在过去的十年中，养殖鱼类的消费者消费量已经增加了，现在英国每天都在食用100万个鲑鱼餐。在影响行业可持续性的各种因素中，鱼类健康是许多特别关注的疾病问题的关键。因此，必须获得可持续的水产养殖业卫生管理，这是该管理的核心是开发新的疫苗，这些疫苗需要进行彻底的测试才能进行销售。这涉及大量暴露于疾病药物的鱼，其中死亡率用作测试疫苗功效的终点。一种方法的开发将使研究人员能够更具人性化的疫苗功效，从而大大减少这些试验中鱼类的苦难。通过疫苗接种的保护取决于特定抗体的产生以及介导特定细胞介导的反应的T细胞的激活，能够杀死受感染的宿主细胞并激活非特异性防御​​措施。对这些细胞反应的研究是减少疫苗试验期间鱼类苦难的关键。一些T细胞（T-辅助细胞）释放介质，称为细胞因子，启动和调节宿主反应。可以根据释放的细胞因子产生不同的反应。 The measurement of these molecules after vaccination can be correlated with the protection conferred by immunisation, a well established method used with reasonable success in mammals.In this study we will determine the numbers of cells producing two cytokines (IL-17 and IL-22) in trout, following vaccination against one of two bacterial pathogens (Yersinia ruckeri or Aeromonas salmonicida) and exposure to the homologous或异源病原体。选择了IL-17和IL-22，因为它们与负责保护哺乳动物中这些类型的病原体的T-辅助细胞亚群有关。它们的生产将被评估为保护的体外相关性，结果将更普遍地作为鱼类原理的证明，以开发一种手段来进行大量的疫苗优化，而无需进行致命的挑战实验。通过这种方式，这项工作将有助于减少未来疫苗开发研究中的鱼类苦难。