Vaccine development against carp viruses: Integrating adaptive immunity

In this thesis we report the development and initial testing of vaccines for common carp against Spring Vireamia of Carp Virus (SVCV) and Koi Herpes Virus (KHV), two important diseases of carp. We developed a DNA vaccine against SVCV, encoding the viral glycoprotein (G), and showed that intra-muscular injection of a very low dose (0.1 mg/g of fish) of the vaccine leads to full protection. Using multiple techniques we show that this vaccine induced a strong local (anti-viral) response as well as the induction of a B- and T- cell memory response. After this success we used the same DNA vaccine and in parallel developed recombinant baculoviruses expressing the G protein for oral vaccine delivery, allowing for stress-free vaccination without any local side-effects. The vaccine was encapsulated in alginate microspheres in order to protect it from intestinal degradation. Despite testing various vaccine doses, regimes and a mucosal adjuvant, no protection was obtained. Next to SVCV, we tested a DNA vaccine against KHV, encoding the ORF25 protein, but under the tested conditions the vaccine was not able to confer protection after intra-muscular injection or oral delivery. Given that understanding the adaptive immune response triggered by vaccination is of utmost importance to understand the underlining protective mechanisms, we developed multiple tools to characterize B cell and T cell responses in common carp. Using these new tools, we significantly contributed to the understanding of adaptive immune responses of common carp and especially, their role during infection and after vaccination.