Development of novel oral vaccination s;trategies for Atlantic salmon

养殖三文鱼是苏格兰最大的食品出口商品，零售额达10亿英磅，苏格兰三文鱼出口到60多个国家。三文鱼养殖业雇用了2200多名员工，在2006至2011年间投资超过2.05亿GB，使该行业成为苏格兰经济的主要参与者。世界对动物蛋白日益增长的需求推动了养殖鱼的消费量从80年代初占鱼类总消费量的9%上升到目前的50%，而且这一比例在未来几十年可能会进一步增加。只有减少或消除增加产量的主要瓶颈，包括控制传染病，才有可能生产足够的养殖鱼来满足这一需求。鲑鱼是需要高质量的环境才能最佳生长的鱼，但即使提供了这种环境，偶尔也会出现疾病，由于鱼类死亡和质量下降，可能会损失数千磅。幸运的是，在20世纪80年代末，S制定了一项疾病预防战略：鱼疫苗接种。这一策略非常成功，以至于在水产养殖中使用抗生素几乎已经消失，所有在苏格兰养殖的三文鱼在一生中都将至少接种一次疫苗。虽然这一战略非常成功，但它有两个主要缺点：需要单独接种鱼类疫苗，以及疫苗配方中包含的佐剂的副作用。2011年，仅在苏格兰就有近5000万条鱼接种了疫苗。这是一个非常昂贵的过程，此外还会造成相当大的压力，使鱼类容易感染其他疾病，只能在它们被运往海洋之前使用。油基佐剂的副作用通常包括腹膜周腔内的局部炎症，这可能会影响生长并降低菲里氏价值。为了解决这一问题，我们建议开展研究，允许发展鲑鱼口服疫苗。这将包括测试一种基于纳米颗粒的新型口服疫苗递送技术。与注射相比，口服疫苗有几个优点：1)疫苗将被配制到饲料中，便于管理；2)因此避免了处理鱼的压力，并在疫苗接种后需要进行化学处理，以防止机会性病原体；3)在鱼被移到海上后，可以给予额外的剂量。因此，这项技术将有助于使鲑鱼养殖更加高效、可持续，并降低疾病预防的成本。为了实现这一目标，我们将从基础研究开始，研究如何识别外源分子并将其呈现给鲑鱼肠道中的免疫细胞，这是了解口服疫苗效力所需的关键知识。然后，我们将使用现有的使用粘膜递送的商业疫苗来阐明一些疫苗有效性的基因标记，无论是将鱼浸泡在疫苗溶液中作为主要疫苗接种，还是作为口服增强剂给予。最后，我们将评估一种新技术的使用，即基于硅的纳米颗粒，以提供针对大西洋鲑鱼两种商业相关疾病的疫苗：腐殖病和胰腺疾病。随着鲑鱼基因组的完成，我们比以往任何时候都更了解鱼类的免疫力。该项目将利用这些知识对肠道免疫和口服疫苗的几个方面进行开创性的研究，帮助英国的水产养殖业保持可持续发展并在未来几年继续增长。

Farmed salmon is Scotland's number one food export with a retail value >£1billion worldwide, and Scottish salmon isexported to over 60 countries. The Salmon aquaculture industry employs over 2,200 people and has invested over£205million between 2006 and 2011, making this industry a major player in Scotland's economy. The world's increasingdemand for animal protein has pushed the consumption of farmed fish from 9% of total fish consumed in the early 80's tonearly 50% at present, and this is likely to increase further in the coming decades. Producing enough farmed fish to supplythis demand will only be possible if the major bottlenecks to increased production are reduced or removed, and this includesthe control of infectious diseases. Salmon are fish that require a high quality environment for optimal growth but even whenthis is provided, occasionally diseases will arise and thousands of pounds can be lost due to fish mortality and qualitydepreciation. Fortunately in the late 1980's a strategy for disease prevention was established: fish vaccination. Thisstrategy has been so successful that the use of antibiotics in aquaculture has almost disappeared and all the salmon thatare farmed in Scotland will have been vaccinated at least once in their life. Although very successful this strategy has twomain drawbacks: the need for individual fish vaccination and the side-effects of adjuvants included in the vaccineformulations. In 2011 nearly 50 million fish were vaccinated in Scotland alone. This is a very costly process and in additioncauses a significant amount of stress that makes fish susceptible to other diseases and can only be employed before theyare moved to sea. The side-effects from oil-based adjuvants usually include localized inflammation within the peritonealcavity, which can compromise growth and depreciate the fillet value. To overcome this problem we propose to undertakeresearch to allow development of oral vaccination for salmon. This will include testing of a novel oral vaccine deliverytechnology based on nanoparticles. Oral vaccination has several advantages in comparison to injection: 1) the vaccinewould be formulated into the feed, making it easy to administer, 2) the stress of handling the fish is thus avoided and theneed for chemical treatments post-vaccination, to prevent opportunistic pathogens, is avoided, 3) extra doses can be givenafter fish have been moved to sea. Therefore this technology will help make salmon farming more efficient, sustainable, and reduce the cost of disease prevention. To achieve this goal we will start the project with basic researchon how foreign molecules are recognized and presented to immune cells in the gut of salmon, key knowledge required to understand oral vaccine efficacy. We will then elucidate some gene markers of vaccine effectiveness using existingcommercial vaccines that use mucosal delivery, either by immersion of fish in the vaccine solution as a primaryvaccination, or given as oral boosters. Lastly we will evaluate the use of a novel technology, silicon based nanoparticles,to deliver vaccines against two commercially relevant diseases for Atlantic salmon: Furunculosis and Pancreas Disease.With the completion of the salmon genome we know more about fish immunity than ever before. This project will use thisknowledge to undertake ground breaking research on several aspects of gut immunity and oral vaccination, helping theUK's aquaculture industry to remain sustainable and to continue to grow over the coming years.