由于全球变暖，养殖和野生鱼类中新出现的传染病疫情正在增加。因此，对气候驱动疾病出现的可持续和伦理研究需要数据驱动和广泛可获得的方法，明确纳入与温度有关的流行病学动态。该提案的主要目的是为研究人员开发一种优化的实验暴露方案，用于鱼类疫苗开发和疾病监测。学生关注增殖性肾病(PKD)，这是一种气候变化驱动的、全球范围内鲑鱼的严重新发传染病。PKD已经成为威胁英国鳟鱼养殖可持续性的主要寄生虫病之一，也是欧洲褐鳟鱼数量下降的主要原因。PKD的健康后果是严重的——受影响的鱼会出现间质性肾组织的大量增殖、贫血和冷漠，变得更容易受到继发性感染。尽管水产养殖业和野生渔业每年都遭受与PKD相关的重大损失，但目前还没有成功建立起PKD的治疗方法，而且由于缺乏针对实验感染挑战的最佳实践指南，疫苗开发工作受到阻碍。本提议的目的是优化PKD实验挑战模型，以限制在PKD相关研究中使用鱼类作为疾病哨兵。我们建议采用以前开发的方法来实现这一目标:1)通过水采样和环境DNA检测来量化寄生虫剂量;2)通过血清学测量暴露鱼的PKD特异性免疫。这些方法将提供一个新的最佳实践挑战协议和一个监控工具包。 Therefore, this studentship project has outcomes which impact the Reduction and Refinement aspects of the 3Rs principles. Reduction will be achieved by removing the need for sentinel fish and successively exposed fish cohorts during experimental challenge. Refinement is achieved by developing a non-lethal, serology based method of measuring fish immunity, relying on blood samples instead lethal sampling, providing a much more sensitive measure of infection status, and, for the first time, allowing the collection of temporal data on the response of individual fish. This will also reduce the number of fish needed to achieve acceptable sample size in experiments, allowing future scaling up of large field trials during vaccine development work. The combined eDNA and serology provides a unique opportunity to non-lethally track the dynamics of specific immune activity towards the parasite as a strong proxy of immunological memory and protective immunity development. For the first time, we will be able to understand the anti-PKD antibody dynamics in pre-exposed fish that are consistent with sufficient parasite exposure to induce natural protective immunity when re-exposed the following year. The use of non-lethally sampled fish during preexposure and re-exposure will enable the tracking of antibody responses in individual fish in order to understand the relationship between antibody dynamics of fish when first exposed to parasites and how antibody levels change during reexposure and how this links to efficient natural protective immunity. In addition to research, PKD clearly affects fish health throughout the salmonid aquaculture industry; 4-4.5M trout annually in the UK are exposed to PKD using the challenge model we propose to improve. If successful, our proposed approaches could significantly reduce the numbers of fish suffering severe PKD on farms (up to 300,000 trout per growing season in the UK die of PKD despite pre-exposure programs). To facilitate research uptake of our protocols, we work with fish health professionals, linking the detailed experimental data with the commercial stocks, which allows benchmarking our results to the current best-practise on farms.
