Fish vaccine development

Maybe not everybody realizes but fish are the earliest vertebrates to have developed an immune system which very much resembles the one of mammals, characterized by an innate and an adaptive branch as well as by specificity and memory. I have always had an interest in the evolution of the vertebrate’s immune system and, in particular, in the immune system of fish. Already during my MSc thesis in Italy I worked on the immune system of sea bass and when I moved to The Netherlands for my PhD I continued working on the immune system of fish, in this case, common carp.

I was initially appointed on a Research Training Network (PARITY) and subsequently on an integrated project, IMAQUANIM, both financed by the European Community. During my PhD I studied innate and adaptive immune reactions in carp against two natural infections caused by the parasite Trypanoplasma borreli and by the Spring Viraemia of Carp Virus (SVCV). In October 2009 I defended my PhD (cum laude) and in January 2011 I have been awarded a Veni grant by the Dutch Organisation for Scientific Research (NWO).

1. Evolution of the vertebrate’s immune system

I am convinced that there is no applied science without fundamental science! We need to keep on addressing fundamental questions on the fish immune system before we can apply this knowledge for future vaccine development in the aquaculture sector. Do fish have Th1, Th2, Th17, Treg cells? Is the biological activity of immune mediators (cytokines, chemokines, etc) conserved throughout evolution? How does the heterothermic nature of fish influence the quality and magnitude of their (memory) immune response? Etc…

2. Fish Immunity to viruses and Vaccine development

Most might be familiar with the idea that fish can get sick but it may come as a surprise that, similar to humans, fish can be vaccinated! My aim is to use the knowledge acquired through fundamental research to develop vaccination strategies against deadly (viral) diseases of carp using the newest vaccination methods. Recombinant live attenuated viruses may be cumbersome to produce but often give excellent protection. DNA vaccines represent the third generation of vaccines and have proven very efficacious in fish. Finding the best routes of administration, e.g. by oral route or bath, is very important because the injection of individual fish, considering the millions of fish produced each year, is not always stress-free, nor cost-effective.

Carp (Cyprinus carpio), which are many angler’s dream are, in fact, the most cultured fish species in the world. On top of this, ‘Koi’, the colourful variety of common carp and most appreciated as pet animal in outdoor water gardens, with some individuals exceeding €100.000 in value, may be the most expensive fish in the world. However, deadly diseases caused by spring viraemia of carp virus (SVCV) and koi herpes virus (KHV) threaten the health of (koi) carp. This is why carp is the target of our vaccine development.

Zebrafish (Danio rerio) belong to the same family (Cyprinidae) and are, in fact, so closely related to carp that their genes can be up to 96% identical. The main advantage of the zebrafish for studying infectious diseases lies in the excellent possibilities for in vivo imaging of host-pathogen interactions, for example using transgenic reporter lines expressing fluorescent proteins in different immune cell types. Their short generation time and high quality genome sequence enable the rapid accumulation of loss- or gain-of-function mutants using forward or reverse genetic screening. Morpholino technology provides an efficient tool for transient gene knockdown in embryos up to the larval stages.

The large carp is perfect for cellular studies whereas the small zebrafish is an excellent tool for genetic studies. Together they form a perfect match to address fundamental questions on the evolution of the immune system and to design novel vaccine approaches.