ReviewA comparative review on European-farmed finfish RNA viruses and their vaccines
Section snippets
Major European diseases affecting farmed finfish caused by RNA viruses
The most important finfish production by European aquaculture involves 6 fish species (Fig. 1) distributed among different geographical locations (Fig. 2). Thus during the last ∼10 years the highest annual productions were of Atlantic salmon Salmo salar (∼900 kt/year), rainbow trout Oncorhynchus mykiss (∼320 kt/year), sea bream Sparus aurata (∼150 kt/year), sea bass Dicentrarchus labrax (∼140 kt/year), carp Cyprinus carpio (∼70 kt/year) and turbot Scophthalmus maximus (∼10 kt/year). While the
Viral nervous necrosis viruses (VNNV)
Fish viruses causing viral encephalopathy and retinopathy (VER), also known as viral nervous necrosis (VNN), have been isolated from more than 35 finfish species, many of them important to the European aquaculture industry such as sea bass and sea bream [5], [6]. Because they can spread both horizontally and vertically from mother to offspring, early prophylaxis was focused on preventing transmission from broodstock fish to eggs/larvae [7]. Thus, in acute juvenile infections of sea bass or sea
Infectious pancreatic necrosis viruses (IPNV)
IPNV are one of the most widely distributed virus affecting most of the farmed finfish species, causing high mortality in recently hatched salmonids, and high worldwide economic losses in juvenile salmon when they are transferred from fresh to sea water. Furthermore, the wide presence of IPNV in asymptomatic adult carriers surviving the disease, contributes to their spreading, interferes with other diseases [29] and is a problem for the correct evaluation of the efficacy of vaccines during
Viral haemorrhagic septicemia viruses (VHSV) and infectious haematopoietic necrosis viruses (IHNV)
Isolated from more than ∼50 fish species from North America, Asia and Europe, from ∼15 different commercialized fish species such as salmonids and flatfish [53] and from an increasing number of free-living marine fish species [3], VHSV cause the highest economic impact in European trout farming. Furthermore, during the last ∼10 years, the VHSV-related infectious haematopoietic necrosis viruses (IHNV), originated in North America have been increasingly isolated in Europe [70], [72].
VHSV and IHNV
Spring viremia of carp viruses (SVCV)
SVCV affect all farmed carp species in Europe, where it causes significant morbidity and mortality typically at spring [116], [117].
SVCV contain a negative-stranded RNA genome coding for L polymerase, N nucleocapsid, G glycoprotein and P and M matrix protein genes but they have no NV protein gene [118] (Table 1).
As VHSV and IHNV, SVCV belong to the Rhabdoviridae family but because they lack the NV gene they have been classified among the Vesiculovirus genus with the vesicular stomatitis Indiana
Salmonid alphaviruses (SAV)
Both salmon pancreas disease (PD) of Atlantic salmon in Norway, Ireland, Scotland and Canada [128] and trout sleeping disease (SD)[129] of rainbow trout in France and Italy are caused by salmonid alphaviruses (SAV).
SAV are enveloped spherical viruses with a positive single stranded RNA genome of ∼12 kb, coding for capsid glycoproteins (E1, E2, E3 and 6K) and non-structural proteins (nsP1–4) [130] (Table 1). E1 and E2 form heterodimer glycoprotein spikes protruding from the SAV membrane. After
Infectious salmon anaemia viruses (ISAV)
ISAV cause 15–100% mortalities in Atlantic salmon, thus producing severe economic losses to the greatest finfish farmed product in Europe. Furthermore, their economic impact was high because European vaccination was only allowed recently, while the first applied control strategy was to stamp out all fish diagnosed with ISA. First detected in Norway in 1984, ISAV has been isolated from Atlantic salmon in Canada, USA and Scotland and from coho salmon (Oncorhynchus kisutch) in Chile [136]. Because
Technological alternatives for viral fish vaccines
In the absence of any existent therapeutic methods and because farmed finfish can develop long-term acquired immunity, viral disease prevention by vaccination is considered one of the most viable strategies to control these diseases [148], [149].
Ideally, a viral vaccine should mimic natural viral infections to induce the proper immune response without causing the disease. Thus compared to other alternatives, live-attenuated viral fish vaccines have many advantages, because they not only induce
Alternative methods to deliver viral vaccines to the fish
Fish can be vaccinated either by injection (i.p or i.m) fish-to-fish or by mass delivery (immersion or oral administration) methods [153]. These alternatives have different advantages and disadvantages with respect to their level of protection, side-effects, practicality and cost efficiency, depending on the size of the fish to be vaccinated and the specific virus. Of all the possibilities mentioned above, only the i.p. (i.e., oil-adjuvanted VP2 IPNV recombinant protein) or i.m. (i.e., G IHNV
Comparative overview of the DNA vaccines against finfish RNA viruses
In spite of the amount of research performed, few fish viral DNA vaccines are commercialized. No live attenuated vaccines are currently licensed, and only one is a DNA vaccine. Thus, most of fish viral vaccines for sale (Table 5) and/or their corresponding patents (Table 6) are based upon inactivated virus or viral recombinant proteins delivered by i.p. injection in oil-adjuvants. For instance, inactivated vaccines against IPNV are being used in salmon culture, despite the fact that not all
Safety/regulatory aspects of fish DNA vaccines
Since fish DNA vaccines have not been licensed in Europe, their safety requirements will need to be regulated based on the previous general rules for DNA vaccines of the European Agency for Evaluation of Medical Products. However, some issues are specific of fish, for instance, the differentiation between a DNA-vaccinated fish and a genetically modified organism (GMO) needs to be further clarified, since different national regulatory organizations maintain different criteria. Thus, the British
Conclusions
Intensive aquaculture is growing more rapidly than all other food animal-producing sectors. To achieve higher levels of production, their viral disease problems must be addressed, since viral outbreaks cause high mortality, severe economical losses and important ecological impacts. An intensive aquaculture, without prevention of the spreading of the viruses they generate, will be unsustainable [167]. However, there are not yet any effective treatments other than destroying all fish in infected
Acknowledgements
Thanks are due to Dr. Espen Rimstad and Fernando Torrent by their helpful commentaries. This work was supported by CICYT projects AGL08-03519-CO4-ACU and INGENIO 2010 CONSOLIDER 2007-00002 of the Ministerio de Ciencia e Innovación of Spain.
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