Development of an immersion vaccine for salmonids

Lead Research Organisation: University of Aberdeen
Department Name: Sch of Medicine, Medical Sci & Nutrition

Abstract

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.

Planned Impact

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.

Therefore, the main output of this Innovation Project is to establish whether the immersion vaccination method can provide immunity to economically important pathogens of salmon. Our ultimate goal is to vaccinate fish (through immersion) only once (but maybe two vaccination rounds are needed to give best protection) with a combination of relevant antigens to provide protection against viral, bacterial and parasite diseases found in aquaculture at present. Benchmark Animal Health Ltd (BAHL) has several suitable antigens of a range of pathogens available of which we initially will test three for validation of the immersion vaccination technique following fish challenge experiments.

We will optimise the best method to produce the vaccine in large quantities and we will confirm whether we can re-use and also inactivate the vaccine (with Pulcea Ltd.) to allow approval by the various legislative bodies for use in recirculating water systems in fish farms. Following future identification of suitable antigens of parasites by BAHL and the UoA, a combined immersion vaccine could in principle incorporate any target antigens including viral, bacterial and parasites.

The potential impact of a combined immersion vaccine for finfish is "aquaculture industry-transformational" as fish vaccination by needle can be eliminated, which will greatly increase the welfare of the fish, minimise fish losses and thus financial losses in the aquaculture business worldwide.
 
Description The grant is officially finished now but the work is still ongoing.
We have made some very interesting observations that we can not fully report here for commercial reasons
An extensive fish vaccination and challenge trial is under way and the results are expected to be completed by the end of 2020.
Early indications are very promising.
Exploitation Route Novel fish vaccination method that would allow fish farmers to vaccinate fish without needle based injection, which will result in less stress for the fish.
Sectors Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The commercial partners are currently exploiting the results of this project. At the moment we can not report on the main findings because possible patents are being considered.
Sector Agriculture, Food and Drink
Impact Types Economic

 
Description BBSRC-LINK
Amount £1,200,000 (GBP)
Funding ID BB/P020224/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 06/2017 
End 05/2020
 
Title immersion vaccination 
Description We have been developing an immersion vaccine method for salmonid fish 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2018 
Provided To Others? No  
Impact The method of immersion vaccination needs to be further optimised before we can report here in detail. Also a patent will be filed and this prevents us from further reporting here at this stage. 
 
Title Fish vaccine 
Description A composition comprising a translocation sequence derived from a fish pathogen and a heterologous payload coupled to the translocation sequence is provided. The composition is able to translocate across the plasma membrane of a eukaryotic cell, for example a fish cell, and thus stimulate an immune response. Accordingly, nucleic acids, vectors, host cells, compositions and vaccines based thereon are also provided. 
IP Reference WO2014191759 
Protection Patent application published
Year Protection Granted 2014
Licensed Commercial In Confidence
Impact Patent gave us the opportunity to submit a new grant to perform proof of concept studies
 
Description Cafe Scientifique 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I presented our work on Saprolegnia infections in salmon farms and how we are looking into new methods too control saprolegniosis and other fish diseases.
Year(s) Of Engagement Activity 2018
 
Description Organising Microbiology School lectures at University of Aberdeen 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Every year I am organising a school lecture for secondary school children to learn about microbiology and show them a career option in sciences and in particular microbiology. Usually we get 100-250 children attending between the ages of 16-18 from several regional schools (Aberdeenshire)
Year(s) Of Engagement Activity 2008,2009,2010,2011,2012,2013,2014,2015,2016,2017