When Dr Stanisaw Snieszko and colleagues injected carp with the first fish vaccine in the late 1930s, they declared that although effective, immunisation was too complicated and time consuming for large scale application in fish farms. Jump forward to today, and vaccines are available for 17 different kinds of fish species, protecting them against 22 different bacterial and 6 different viral diseases.
Developing fish vaccines is challenging, but as Dr Maryam Dadar (Razi Vaccine and Serum Research Institute in Iran) and colleagues highlight in a paper recently published in Reviews in Fisheries Science & Aquaculture, significant progress is being made.
Vaccines typically come in one of two different flavours – inactivated vaccines and attenuated vaccines. Both involve giving the fish a dose of the pathogen we want to protect the fish against, but inactive vaccines use dead pathogens whilst attenuated vaccines use live pathogens, albeit in a weakened form so they don’t actually cause illness.
Attenuated vaccines can provide better immunity than inactivated vaccines, and can also be used to treat young fish (by immersion).
However since they use a live pathogen, there is a small risk that some residual virulence may remain and the treated animal – or those that come in contact with the animal, could become infected.
Unsurprising that attenuated vaccines in particular must undergo rigorous testing – including evaluation of the risk of infection - before they are licenced. Most licenced vaccines available to aquaculturalists are inactivated vaccines.
Traditional vaccines can be time consuming to develop, which limits their usefulness in preventing the spread of newly emerging pathogens. Thanks to advances in fields such as genetics, immunology, and biotechnology, new methods for fish vaccines have emerged in recent years that can be developed and produced over much faster time frames. These methods include DNA vaccines, recombinant vaccines, and using genetically engineering vectors.
DNA Vaccines are still in the developmental phase. They involve injecting fish with DNA from the pathogen that we want to protect them against, either alone or with a vector that contains the DNA.
Once in the fish, this DNA then produces proteins from the pathogen (‘antigens’), which in turn triggers the fish’s immune system. Since the fish are never given the pathogen itself, there is no risk of infection. What’s more, DNA vaccines are very stable and don’t need to be kept cold, making transport and storage easier than traditional vaccines which require much more care. If they are developed and licenced for use, they should also be relatively cheap and quick to produce. Perhaps more importantly, they could produce strong, long-lived immune responses. More work is needed to understand their drawbacks, such as the potential for the fish’s immune system to become tolerant to the antigens.
Recombinant vaccines also take advantage of antigens, but use an attenuated bacteria or virus as a vector to carry the antigen from the pathogen you want to protect the fish against. As with DNA vaccines, the fish is never actually given the pathogen so there is no chance of infection. Alongside The advantage of recombinant vaccines is that they mimic naturally-occurring infections very well, which helps produce a strong immune response in the treated fish. They can also be produced fairly easily on a large scale.
Since vectors can pose risks in themselves, research into developing engineered vectors to carry pathogens in vaccines is under way. Engineered vectors could be used in emerging vaccines such as recombinant vaccines, as well as for the more traditional attenuated vaccine which themselves may be subject to genetic engineering. Genetically attenuated vaccines operate in the same way as traditional attenuated vaccines, but rather than treat a pathogen to weaken it, the pathogen is engineered to be weak.
At the present time, vaccines are either delivered orally, via injection, or by immersing the fish in, or spraying the fish with, a vaccine. With fish farms typically containing large volumes of individuals which need vaccinating, this can be a time-consuming process. Finding more practical solutions to delivering vaccines is also gaining a lot of attention – including the use of plant-based edible vaccines. These edible vaccines are still in the developmental stage, but the idea is that they could be incorporated into fish feed, potentially acting as boosters, or potentially even vaccines in its own right. The idea potentially has a number of benefits. They don’t use live pathogens, don’t require to be kept cold, are much less labour intensive to administer than current methods, and the fish themselves would arguably find the whole ordeal much less stressful.
Each of these new vaccines faces their own challenges, though perhaps one common to all is how they are created. Each of these methods involves genetically engineering organisms. Fish treated with DNA, recombinant, or even edible vaccines, and even more traditional attenuated vaccines that use genetically engineered vectors may be considered genetically modified organisms (GMOs) in their own right. This presents two primary issues. First, there are concerns surrounding the impact of genetically modified pathogens or vectors that make their way into the environment. This is a particular stumbling block for genetically engineered attenuated vaccines, which as a result are not gaining much ground for aquaculture use. Second, in many countries there is strong public opposition to GMOs for human consumption. It may simply not be commercially viable to use these types of vaccines in aquaculture at the moment.