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A Systematic Approach towards Optimizing a Cohabitation Challenge Model for Infectious Pancreatic Necrosis Virus in Atlantic Salmon (Salmo salar L.)

机译:优化大西洋鲑(Salmo salar L.)传染性胰腺坏死病毒的同居攻击模型的系统方法

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摘要

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 1x107 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.
机译:建立了同居挑战模型,用于通过逐步方法评估针对大西洋鲑(Salmo salar L)中的传染性胰腺坏死病毒(IPNV)开发的疫苗的功效。该研究涉及确定一组输入变量,这些变量在包含在模型中之前已进行了优化。确定的输入变量包括编码T217A221母题的高毒力挪威Sp株NVI015-TA,其具有导致> 90%的死亡率的能力和490.18(p <0.000)的危险风险比用作挑战病毒。每条鱼的攻击剂量估计为TCID50 / mL,为1x10 7 TCID50 / mL,而病毒脱落物的比例估计为每只鱼总数的12.5%。该模型是基于三个平行的水箱系统设计的,其中使用Cox危险比例回归模型来估计显示每个水箱中接种鱼和对照鱼之间的显着差异所需的最小鱼类数量。优化所有输入变量,以在未接种鱼中产生> 75%的死亡率,从而在接种鱼和对照鱼之间获得较高的区分能力(DC),以此作为疫苗效力的量度。该模型通过显示高易感鱼与未接种疫苗的对照鱼相比,具有更高的区分受疫苗保护的鱼和未接种疫苗的对照鱼的DC,从而显示了在挑战模型优化中使用对IPNV高易感鱼的重要性。一旦优化了所有输入变量,就可以通过使用相同输入变量的三个独立的同居挑战试验产生相似的结果来测试模型的可重复性。总体而言,此处提供的数据表明,该研究中开发的同居挑战模型是可重现的,并且可以可靠地用于评估针对IPNV疫苗开发的大西洋鲑鱼疫苗的功效。我们预想,这里使用的方法将为开发用于评估水产养殖中使用的不同疫苗效力的最佳挑战模型开辟新途径。

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