Innate immune responses to fish viruses

Experimental vaccines need to be thoroughly validated prior to commercialization. Validation of vaccines relies on aspects related to safety and efficacy. The latter aspect is normally evaluated by efficacy trials which normally include the exposure of the fish to the natural pathogen. From an animal welfare point of view it would be ideal to be able to predict the efficacy of a vaccine without challenging the fish. This can be achieved by defining correlates of protection. Correlates of protection ‘are laboratory parameters which are associated with protection from the occurrence of clinical disease, as shown after sufficient and controlled trials’ (FDA)1. Recently our group reported the development of an intramuscular DNA vaccine against Spring Viremia of Carp virus (SVCV), which was shown to confer up to 100% protection to carp even at a single dose of 0.1 µg DNA/g of fish. A further characterization of the mechanisms underlining protection, revealed the presence of serum neutralizing antibodies and of memory T cells in vaccinated animals. Neutralizing titres and memory T cells can therefore be considered preliminary correlates of protection upon DNA vaccination of carp against SVCV. Nevertheless, with the current tools, it was not possible to determine which type of immunoglobulin (Igm, IgD, IgT1, IgT2 or all) contributed to the serum neutralizing titres, nor which type of T cells (CD4+, CD8a+ or both) contributed to the memory response. The optimal vaccine dose and corresponding duration of protection was also not assessed. additionally, our group previously developed a monoclonal antibody (WCL38) recognizing putative mucosal T cells. The antibody requires further characterization but is an excellent addition to the current panel of tools and will be instrumental to characterize mucosal responses. Therefore, the ultimate goal of this project is to characterize adaptive immune responses to SVCV-G DNA vaccination, to ultimately define correlates of protection. The specific objectives of this project are: 1- develop and validate tools to study B and T cell responses after infection and/or vaccination. 2- characterize systemic as well as mucosal B and T cell responses after injection and/or oral vaccination. 3- define correlates of protection upon vaccination