title: A Systematic Approach towards Optimizing a Cohabitation Challenge Model for Infectious Pancreatic Necrosis Virus in Atlantic Salmon (Salmo salar L.).
abstract: A cohabitation challenge model was developed for use in evaluating the efficacy of vaccines developed against infectious pancreatic necrosis virus (IPNV) in Atlantic salmon (Salmo salar L) using a stepwise approach. The study involved identifying a set of input variables that were optimized before inclusion in the model. Input variables identified included the highly virulent Norwegian Sp strain NVI015-TA encoding the T217A221 motif having the ability to cause >90% mortality and a hazard risk ratio of 490.18 (p<0.000) for use as challenge virus. The challenge dose was estimated at 1x10(7) TCID50/mL per fish while the proportion of virus shedders was estimated at 12.5% of the total number of fish per tank. The model was designed based on a three parallel tank system in which the Cox hazard proportional regression model was used to estimate the minimum number of fish required to show significant differences between the vaccinated and control fish in each tank. All input variables were optimized to generate mortality >75% in the unvaccinated fish in order to attain a high discriminatory capacity (DC) between the vaccinated and control fish as a measure of vaccine efficacy. The model shows the importance of using highly susceptible fish to IPNV in the optimization of challenge models by showing that highly susceptible fish had a better DC of differentiating vaccine protected fish from the unvaccinated control fish than the less susceptible fish. Once all input variables were optimized, the model was tested for its reproducibility by generating similar results from three independent cohabitation challenge trials using the same input variables. Overall, data presented here show that the cohabitation challenge model developed in this study is reproducible and that it can reliably be used to evaluate the efficacy of vaccines developed against IPNV in Atlantic salmon. We envision that the approach used here will open new avenues for developing optimal challenge models for use in evaluating the efficacy of different vaccines used in aquaculture.
authors.affiliation: Norwegian University of Life Sciences, Faculty of Veterinary Medicine and Biosciences, Department of Basic Sciences and Aquatic Medicine, Section of Aquatic Medicine and Nutrition, Ullevålsveien 72, Oslo, Norway.
authors.forename: Hetron Mweemba
authors.initials: HM
authors.lastname: Munang'andu
authors.affiliation: AquaGen, Trondheim, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Santi
authors.affiliation: PHARMAQ AS, Harbitzalléen 2A, 0275, Oslo, Norway.
authors.forename: Børge Nilsen
authors.initials: BN
authors.lastname: Fredriksen
authors.affiliation: PHARMAQ AS, Harbitzalléen 2A, 0275, Oslo, Norway.
authors.forename: Knut-Egil
authors.initials: KE
authors.lastname: Løkling
authors.affiliation: Norwegian University of Life Sciences, Faculty of Veterinary Medicine and Biosciences, Department of Basic Sciences and Aquatic Medicine, Section of Aquatic Medicine and Nutrition, Ullevålsveien 72, Oslo, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Evensen
mesh_terms: D000818:Animals; D018175:Birnaviridae Infections / Q000662:veterinary*; D004198:Disease Susceptibility; D005393:Fish Diseases / Q000401:mortality / Q000517:prevention & control* / Q000821:virology*; D018061:Infectious pancreatic necrosis virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D008962:Models, Theoretical; D015203:Reproducibility of Results; D020317:Salmo salar / Q000276:immunology* / Q000821:virology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D014765:Viral Vaccines