Wetenschap - 15 november 2012

Swimming in vaccine

With the worldwide growth of commercial fish farming, the demand for good vaccination procedures is growing too. A large European research project is developing new vaccines, but must first answer the question of how they can best be administered. Wageningen immunologist Geert Wiegertjes is in the driving seat.


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Farmed fish is an increasingly important source of protein. Worldwide 63 million tons of farmed fish are produced, equalling the amount of wild-caught fish from the sea. And now the outlook for the traditional fisheries is bleak, due to falling fish stocks and the quotas that are a response to them.
But fish farming is not without its problems either. As in intensive livestock farming, harmful bacteria and viruses can spread easily in fish ponds. And because antibiotics are unacceptable, vaccines are needed. They are already in use in the lucrative Norwegian salmon farming sector, where salmon are injected either mechanically or by hand on a conveyor belt. But this is an expensive process and not good for the wellbeing of the fish - a consideration which is gaining in importance in this sector.
The alternative would be to administer the vaccine in the water or in the fish feed. That sounds logical enough, but there are countless objections to it in practice. How do you make sure each fish gets the right amount and that it goes to the right part of its body? How do you prevent the vaccine from spreading beyond the fish pond? These are some of the questions to be addressed in the next few years by 30 European research institutes led by Wageningen immunologist Geert Wiegertjes. A sum of 6 million euros has been allocated to the programme, which goes by the name of TargetFish and started at the beginning of November.
Bucket of vaccine 
The immune system of the fish is very similar to the human one, claims Wiegertjes. 'Just like ours, a fish's immune system has a memory, so it can recognize pathogens and make antibodies.' This means that for fish, as for humans, you can make a vaccine by administering an inactive version of the pathogen or a protein from it.
Intensive salmon fish farmers in Norway are leading the way. In the nineteen seventies large amounts of antibiotics were used in this industry, until the first vaccines were discovered. 'If you killed the pathogenic bacteria and put them in a bucket of water, the fish in the bucket absorbed the bacteria and were immunized,' says Wiegertjes. 'That went well with several troublesome bacteria but it didn't work for all pathogens.' Unlike what happens in humans, in fish most bacteria and viruses get in through the skin. This makes the layer of slime on a fish's skin an important factor. 'If we succeed in getting more antibodies into the slime layer, it will be very effective,' says Wiegertjes. A main objective of TargetFish, in his view, is to find out whether vaccines in the feed and the water lead to more immunity in the slime layer.

DNA vaccine
Besides research into the possibilities for administering a vaccine, the researchers are also looking at whether protein vaccines could perhaps be replaced by DNA vaccines. 'If you do this you exchange the protein for the gene that manufactures the protein. The fish's cells then take care of the gene expression. That works very well for certain viral diseases,' says Wiegertjes. This method is already in use in Canada, but European countries are cautious about it. The researchers want to find out whether DNA vaccines can be used safely. They are collaborating on this with biotech companies which can help to create the vaccines. Most of the companies have already been bought up by the pharmaceutical industry, including Dutch company Intervet, now part of MSD. These companies are often wary of using DNA vaccines, says Wiegertjes. 'They are afraid of losing their good name.'
Koi carp
The 30 participating research institutions have divided up the tasks. Some will be working on the development of new vaccines, while others work on how they could be administered. The Wageningen group will focus on vaccines for carp, which is mainly farmed in large ponds in eastern Europe. Because the market value of an individual carp is much lower than that of the salmon, vaccination with a syringe is not cost-effective. 'In this case we have to vaccinate through the feed,' Wiegertjes asserts. The standard carp is rarely vaccinated at present, but its exotic cousin, the koi carp, is. The koi carp fetches high prices as a decorative fish, making vaccine that is injected a worthwhile investment. 'But it is still not done as well as it might be; the vaccine can be improved,' says Wiegertjes. The Wageningen group is going to work on this together with a partner from Israel, where there are many koi carp breeders. They are helped by the fact that Cell biology and Immunology unravelled the genome of the carp this year, working together with Leiden researchers. 'We can now find out in detail which receptors need to be switched on in the fish in order to recognize diseases. That gives us a lot of knowledge about their immune system and the development of better vaccines.' With the European funding, Wiegertjes' group can employ one PhD student and one postdoc for one and a half years.
Cheap imports
The fish farming sector in the Netherlands is still of modest proportions. Dutch fish farmers mainly breed eel and catfish in covered ponds, to the tune of 10,000 tonnes per year in total. But in other European countries, farming of salmon, trout, sea bass, sea bream, turbot and carp has really taken off. These European fish farmers have to compete with cheap imports of tilapia and pangasius from Asia. Worldwide there are now 63 million tonnes of farmed fish being kept in freshwater ponds and in cages in the sea - about as much as is caught from the sea.