Development of a mucosal adjuvant for fish vaccination

水产养殖业是增长最快的部门之一，为不断扩大的世界人口提供食物。全世界人类消费的鱼中已有约50%是水产养殖生产的，这一数字预计还会进一步上升。与其他食品生产部门一样，水产养殖业的可持续性取决于对鱼类健康的良好管理和对疾病的有效控制。传染病的暴发可能导致严重的经济损失，可能需要多年才能恢复。在过去的30年里，疫苗接种已成为提高鱼类对细菌的抵抗力的重要手段，并显著减少了养鱼中抗生素和有毒化学品的使用，在该行业的环境影响以及改善鱼类健康方面带来了巨大的好处。预防疾病的最有效方法是通过腹腔注射接种疫苗，部分原因是抗原可以随着油基佐剂的加入而缓慢释放，以激活免疫系统。尽管这种方法具有极好的保护效果，但它会给鱼带来压力，是劳动密集型的，而且可能会引起不必要的副作用，如腹膜粘连、肉芽肿甚至自身免疫。然而，浸泡疫苗接种，只需将鱼放入稀释疫苗的溶液中，已被证明对鱼有效，但迄今仅限于几种细菌病原体，通常需要增强剂才能完全保护，限制了其使用。对有效佐剂的需求在很大程度上推动了注射疫苗接种，这需要随着几种用于哺乳动物/人类的高效粘膜佐剂的出现而重新考虑。通过将牛津大学的世界领先的粘膜佐剂小组与阿伯丁的世界领先的鱼类免疫学小组联系起来，这项提案计划优化Sattentau教授开发的一种用于鱼类的新型粘膜佐剂的使用。首先，我们将制备稳定的配方，其中含有一种被杀死的细菌病原体(伊尔森氏菌)，适合在鱼身上进行测试。我们将使用三种不同佐剂使用量的配方，并将在鱼(彩虹鲑鱼)中引发的反应与商业浸泡疫苗对这种疾病的反应进行比较。我们将研究增强一些重要免疫基因表达的能力，这些基因被认为与保护性反应有关，以及血液抗体水平。我们将根据引起的反应选择最佳配方，用于下一步的实验，即给鱼接种疫苗，然后将其暴露在活的病原体中，看看这些反应是否具有良好的保护/免疫力。如果成功，这一结果将有可能彻底改变鱼的浸泡疫苗接种。用有效的粘膜佐剂获得增强的免疫反应/保护，可避免在浸泡疫苗接种后加强接种疫苗的需要，或允许对目前需要辅助性IP注射疫苗的疾病诱导保护性反应。我们相信，这种方法有能力改变鱼的浸泡(粘膜)疫苗接种技术。

Aquaculture is one of the fastest growing sectors that provide food to the expanding world population. Already ~50% of fish consumed by humans worldwide is produced in aquaculture, and this figure is projected to rise further. Like other food producing sectors, the sustainability of the aquaculture industry relies on good management of fish health and effective control of diseases. Outbreaks of infectious diseases can lead to heavy economic losses which may require many years to recover. During the last 30 years, vaccination has become an important means to improve fish resistance to bacteria, and has allowed a significant reduction in the use of antibiotics and toxic chemicals in fish farming, with tremendous benefits in terms of the environmental impact of the industry as well as improved fish health. The most effective way to achieve protection against diseases is to administer vaccines via intraperitoneal injection, partly due to the fact that antigens can be slowly released with the addition of oil based adjuvants for activation of the immune system. Despite the superior protection, this method causes stress to the fish, is labour intensive and can induce unwanted side-effects such as peritoneal adhesions, granulomas and even autoimmunity. However, immersion vaccination, where the fish are simply placed into a solution of diluted vaccine, has been shown to work in fish but to date is limited to a couple of bacterial pathogens and typically requires boosters for full protection, limiting its use. The need for effective adjuvants has largely driven injection vaccination, and this needs to be revisited with the appearance of several highly efficacious mucosal adjuvants being developed for use in mammals/humans. By linking a world leading mucosal adjuvant group at Oxford and a world leading fish immunology group at Aberdeen, this proposal plans to optimise the use of a novel mucosal adjuvant for use in fish, that has been developed by Professor Sattentau. Initially we will prepare stable formulations containing a killed bacterial pathogen (Yersinia ruckeri), that are suitable for testing in fish. We will use three formulations that vary in terms of the amount of adjuvant being used, and will compare the responses elicited in the fish (rainbow trout) with those elicited by a commercial immersion vaccine to this disease. We will examine the ability to enhance the expression of a number of important immune genes, thought to be involved in protective responses, as well as blood antibody levels. We will select the best formulation in terms of the responses elicited, to be used in a further experiment where the fish will be vaccinated and then exposed to the live pathogen, to see if the responses give good protection/immunity. If successful the results would have the potential to revolutionise immersion vaccination of fish. Enhanced immune responses/protection obtained with effective mucosal adjuvants may avoid the need for booster vaccination following immersion vaccination, or allow protective responses to be induced to diseases that currently require adjuvanted IP injection vaccination. We believe such an approach has the capacity for a step change in immersion (mucosal) vaccination technology for fish.