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.

在过去的二十年里，英国的鱼类养殖业急剧增长。苏格兰目前生产超过13万吨大西洋鲑鱼，是全球第三大养殖鲑鱼生产国。英国每年还生产约16，000吨虹鳟鱼。在过去的十年里，消费者对养殖鱼类的消费量增加了两倍，现在英国每天要吃掉100万份鲑鱼餐。在影响渔业可持续性的各种因素中，鱼类健康是关键，一些疾病问题特别令人关切。因此，为了实现可持续的水产养殖业，必须进行健康管理，而这种管理的核心是开发新的疫苗，这些疫苗在上市前需要进行彻底的测试。这涉及大量鱼类暴露于病原体，其中死亡率被用作测试疫苗效力的终点。开发一种方法，使研究人员能够更人道地确定疫苗的有效性，将大大减少这些试验中鱼类的痛苦。通过疫苗接种的保护依赖于特异性抗体的产生和介导特异性细胞介导的应答的T细胞的活化，其能够杀死感染的宿主细胞并激活非特异性防御。对这些细胞反应的研究是在疫苗试验期间减少鱼类痛苦的关键。一些T细胞（T辅助细胞）释放称为细胞因子的介质，启动和调节宿主反应。根据释放的细胞因子可以产生不同的应答。在接种后对这些分子的测量可以与免疫所赋予的保护相关联，免疫是一种在哺乳动物中使用并取得合理成功的成熟方法。（IL-17和IL-22），在针对两种细菌病原体之一接种疫苗后，（鲁氏耶尔森氏菌或杀鲑气单胞菌）和暴露于同源或异源病原体。选择IL-17和IL-22是因为它们与负责在哺乳动物中保护免受这些类型的病原体的T辅助细胞亚群相关。它们的生产将作为保护的体外相关性进行评估，结果将更普遍地作为鱼类的原理证明，以期开发一种方法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，这项工作将有助于在未来的疫苗开发研究中减少鱼类的痛苦。