Development of an immersion vaccine for salmonids

鱼类处理和基于注射的疫苗接种是鱼类应激的最大原因之一，并且由于疫苗接种后水霉病和细菌感染的爆发，总是导致死亡率增加。仅在苏格兰，数百万的前鲑鱼（所有孵化鲑鱼的10%）在接受注射疫苗后死于水霉感染。因此，迫切需要开发更好的疫苗接种实践，以提高动物福利并降低死亡率。鱼的浸没疫苗接种是用于证明对细菌性疾病的有效保护的第一种方法，但由于需要包含疫苗佐剂而被注射疫苗接种所取代。如果通过浸没途径可以增强抗原的递送，这显然对完全无菌的鱼类处理具有巨大的希望，从而减少压力并显著降低死亡率。我们的方案的中心假设是，浸泡疫苗与重组SpHtp1偶联抗原可以成功地用于保护鱼类免受疾病。我们的总体目标是开发和商业化的SpHtp1易位机制到鲑鱼和其他养殖鱼类的浸泡疫苗输送方法。我们已经证明，我们的专利方法可以成功有效地将蛋白质导入活鱼。此外，我们还观察到，将鳟鱼浸入融合有mRFP的SpHtp 1溶液中，可以产生特异性抗体。因此，我们的主要产出将是：1）与所选抗原偶联的SpHtp 1的易位肽提供针对鲑鱼水产养殖中关注的疾病的保护的证据，2）优化鱼的免疫应答。3）高效和多产的SpHtp 1重组蛋白过表达方法，我们的商业合作伙伴BAHL和Pulcea Ltd.的疫苗方法的规模化生产和未来商业化4）可在养殖场现场使用的浸泡疫苗的回收和再利用方法所有产出将由BAHL和Pulcea Ltd.开发，以获得商业化的许可和批准，并最终完全用于水产养殖业。基本病原体的抗原已经通过BAHL获得，UoA和BAHL将在未来的项目中寻找更多的抗原。目前的申请雄心勃勃，但可以实现，由于拟议的大量工作，将需要24个月才能完成。总之，鳍鱼浸泡疫苗的潜在影响是“水产养殖行业转型”，因为通过注射接种疫苗的鱼类可能会被淘汰，这将大大增加鱼类的福利，并最大限度地减少鱼类损失，从而最大限度地减少全球水产养殖业务的财务损失。

Fish handling and injection-based vaccination is one of the biggest causes of stress for fish and always results in increased mortality due to post-vaccination outbreaks of saprolegniosis and bacterial infections. In Scotland alone, millions of pre-smolt (10% of all hatched salmon) die due to Saprolegnia infections after receiving an injection-based vaccine. Therefore, there is an urgent need to develop better vaccination practices to increase animal welfare and reduce mortalities. Immersion vaccination of fish was the first method used to demonstrate effective protection against bacterial diseases, but was overtaken by injection vaccination due to the need for inclusion of vaccine adjuvants. Should enhanced delivery of antigens be possible by the immersion route clearly this holds enormous promise to completely obviate fish handling, thus reducing stress and significantly lowering mortality. The central hypothesis of our programme is that immersion vaccination with recombinant SpHtp1-coupled antigens can be used successfully to protect fish against diseases. Our overall objective is to develop and commercialise the SpHtp1 translocation mechanism into an immersion vaccine delivery method for salmonids and other farmed fish. We have already demonstrated that our patented method can be used successfully and effectively in directing proteins into live fish. Furthermore, we have observed specific antibody production in trout that were immersed in a solution of SpHtp1 fused to mRFP.Therefore, our main outputs will be: 1) Evidence that the translocating peptide of SpHtp1 coupled to selected antigens give protection against disease of concern in salmonid aquaculture, in immersion vaccination trial experiments.2) Optimisation of the immune response in fish.3) A highly efficient and productive SpHtp1-recombinant protein overexpression method for large-scale production and future commercialisation of the vaccine method by our commercial partners BAHL and Pulcea Ltd.4) A method to recycle and inactivate the immersion vaccine that can be employed on site in the farm.All outputs will be exploited by BAHL and Pulcea Ltd. in obtaining licenses and approvals for commercialisation and eventually full use by the aquaculture industry. Antigens of essential pathogens are already available through BAHL, and further antigens will be sought in future projects by the UoA and BAHL. The current application is ambitious but achievable and will take 24 months to complete because of the significant amount of work that is proposed. In summary, the potential impact of an immersion vaccine for finfish is "aquaculture industry-transformational" as fish vaccinated by injection could be eliminated, which would greatly increase the welfare of the fish and minimise fish losses and thus financial losses in the aquaculture business worldwide.