Development of a mucosal adjuvant for fish vaccination

鱼类疫苗接种粘膜佐剂的研制

• 批准号: BB/M026302/1
• 负责人: Chris Secombes
• 金额: $ 29.29万
• 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: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM026302%2F1
• 关键词: Development; mucosal; adjuvant; fish; vaccination

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.

水产养殖是增长最快的行业之一，为不断扩大的世界人口提供食物。全球人类消耗的鱼类已经在水产养殖中生产了约50％，而且该数字预计将进一步上升。像其他食品生产部门一样，水产养殖业的可持续性依赖于良好的鱼类健康和有效控制疾病。传染病的爆发可能导致严重的经济损失，这可能需要多年才能康复。在过去的30年中，疫苗接种已成为改善鱼类对细菌耐药性的重要手段，并允许在养鱼中大幅减少抗生素和有毒化学物质的使用，从而在行业的环境影响方面具有巨大好处，并改善了鱼类健康。实现疾病保护的最有效方法是通过腹膜内注射施用疫苗，部分原因是可以通过添加油性佐剂缓慢释放抗原来激活免疫系统。尽管具有优越的保护，但这种方法会给鱼带来压力，它是劳动力密集的，并且可能引起不必要的副作用，例如腹膜粘连，肉芽瘤甚至自身免疫性。但是，仅将鱼简单地放入稀释疫苗的溶液中，浸入浸入疫苗已被证明在鱼中起作用，但迄今为止仅限于几种细菌病原体，通常需要助推器才能得到充分保护，从而限制了其使用。有效的佐剂的需求在很大程度上是导致注射疫苗的，并且需要重新审视这几种高效的粘膜佐剂，以用于哺乳动物/人类。通过将牛津大学世界领先的粘膜佐剂组和阿伯丁世界领先的鱼类免疫学小组联系起来，该提案计划优化使用Sattentau教授开发的新型粘膜佐剂用于鱼类。最初，我们将制备适合在鱼类中进行测试的稳定配方（Yersinia ruckeri）。我们将使用三种与所使用的佐剂量不同的配方，并将将鱼类（彩虹鳟鱼）与商业浸入疫苗引起的反应与这种疾病进行比较。我们将研究增强许多重要免疫基因表达的能力，这些免疫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的配方，以在进一步的实验中使用，在该实验中，将对鱼接种疫苗，然后暴露于活病原体，以查看反应是否提供良好的保护/免疫力。如果成功，结果将有可能彻底改变鱼类的浸入疫苗接种。通过有效的粘膜佐剂获得的增强的免疫反应/保护可能会避免浸入疫苗接种后需要进行促进疫苗接种，或者允许保护性反应被诱导到目前需要辅助IP注射疫苗的疾病。我们认为，这种方法具有浸入式（粘膜）疫苗接种技术的能力。