Fish Virus Vaccines (ViVaFish)

In the VivaFish project, we aim to generate knowledge, tools and methods that will contribute to better vaccines against viral diseases in farmed fish. The viral diseases we focus on are Pancreas disease (PD), Heart and skeletal muscle inflammation (HSMI), Cardiomyopathy (CMS) and Infectious salmon anemia (ISA). Researchers with wide experience in fish virology and - immunology from Norwegian University of Life Sciences, University of Tromsø, Institute of Marine Research and Norwegian Veterinary Institute are a part of Viva Fish. Better control of viral diseases in aquaculture will be a significant contribution to the future ecological, environmental and ethical sustainability. When developing new viral vaccines used a broad approach will be used in VivaFish. An optimal vaccine will first stimulate the fish's innate immune response that will provide a short-term protection while helping to involve the adaptive immune response that again will provide a long-lasting protective immunity. At the same time, there should be minimal side effects due to the vaccination. The cellular adaptive immune response is important for protection against many viral diseases, and it is difficult to initiate such a response using inactivated (killed) vaccines. In VivaFish, we try to produce live attenuated virus variants and self-replicating nucleic acid vaccine, assuming that these will be better suited for achieving prolonged cellular adaptive immune response. However, vaccine models with inactivated whole virus particles, virus like particles (VLPs) and recombinantly produced subunits of the virus will also be tested in combination with various adjuvants and immune signal transmitters in order to achieve better immunity. Studies of interaction between vaccine candidates and the host immune system will be a central theme in Viva Fish platform. It may be a major methodological improvement if one could estimate the degree of long-term protection by characterizing salmon responses after immunization. We have shown that immunization of salmon with plasmids expressing the HE gene of ISAV in combination with plasmids expressing interferon c induce protection against ISA. For Piscine orhtoreovirus we have achieved a detailed description of the acute phase of the replication process; characterized viral factories; studied the influence the virus infection has on the salmon's tolerance against hypoxia;fouind the main target cell for PRV (red blood cell); developed a method to purify the virus and shown that immunization with adjuvanted purified virus induce protection against HSMI. We have further develop a method for a bead-based detection of multiple variants of antibodies. Furthermore, live attenuated, SAV variants have been made; PRV and PMCV antigens have been produced in various expression systems; and vectorised virus and DNA-expression systems have been made for PRV and PMCV. In VivaFish great emphasis is placed on trying to identify functional signature responses which may indicate long-term protection. Such signatures may reduce the number of fish needed in future vaccine testing. Therefore, studies of diversity and specificity of B cells which are involved in long-term protection; phenotypic profiles of salmon antibody responses; and cytotoxic T-cell's ability to control virus infections in salmon, are important parts of Viva Fish. Immunization and subsequent infection experiments for the relevant diseases will be tested when assumed good vaccine candidates are available. Such efforts will not only study the degree of protection, but also include immune response measurements and evaluation of various routes of administration of vaccines, such as by injection or through mucous membranes.

If aquaculture is to be ecologically, environmentally and ethically sustainable in the future, control of viral diseases is essential. ViVaFish will generate new knowledge, tools, and methods relevant for the vaccination of farmed fish against viral disea ses, thus reducing today's shortcomings in viral prophylaxis. Together the principal investigators have extensive experience and an excellent track record in the fields of fish virology and immunology. To develop new vaccines, and improve existing ones, a broad approach will be used where replicating and non-replicating vaccine models administrated parenterally and mucosally will be studied. Furthermore, studies of the interaction between vaccine candidates and the host immune system will be a central th eme of the proposed platform. We will develop a tool-kit containing live attenuated virus vaccines and/or replicons for SPDV, PMCV, PRV and ISAV. Together with traditional inactivated virus vaccines, these will be used to understand the elicited, protecti ve immune responses. Challenge models for all of these viruses have been established by the ViVaFish scientists. We will study how innate signals induced by the vaccine candidates translate into protective immunity and how this can be exploited to design vaccines and adjuvants that promote long-lasting immunity while also reducing or abolishing side effects. Therefore, we believe it is important to characterize the diversity and specificity of the B and T cell responses in salmonids. Molecular and functio nal signatures of protection will be characterized, which will provide a base for the development of reliable in vitro assays that are predictive of protective immunity. Such signatures can be important for further vaccine development, and may reduce the number of experimental fish needed for future vaccine testing. The ViVaFish platform will contribute significantly to the development of technologies that will be instrumental in the control of viral diseases.