Instituto de Virología, CICV y A - INTA, Buenos Aires, Argentina.
Vaccine. 2010 Mar 16;28(13):2539-49. doi: 10.1016/j.vaccine.2010.01.035. Epub 2010 Jan 30.
Infectious Bovine Rhinothracheitis (IBR) caused by bovine herpesvirus 1 (BoHV-1) infection is distributed worldwide. BoHV-1 either alone or in association with other respiratory cattle pathogens causes significant economic losses to the livestock industry. The aim of this work was to validate a guinea pig model as an alternative method to the current BoHV-1 vaccine potency testing in calves. Guinea pigs were immunized with two doses of vaccine, 21 days apart and sampled at 30 days post vaccination (dpv). BoHV-1 antibody (Ab) response to vaccination in guinea pigs, measured by ELISA and virus neutralization (VN), was statistically compared to the Ab response in cattle. The guinea pig model showed a dose-response relationship to the BoVH-1 antigen concentration in the vaccine and it was able to discriminate among vaccines containing 1log(10) difference in its BoHV-1 concentration with very good repeatability and reproducibility (CV < or = 20%). A regression analysis of the Ab titers obtained in guinea pigs and bovines at 30 and 60dpv, respectively, allowed us to classify vaccines in three potency categories: "very satisfactory", "satisfactory" and "unsatisfactory". Bovines immunized with vaccines corresponding to each of these three categories were experimentally challenged with BoVH-1 virus, the level of protection, as measured by reduction of virus shedding and disease severity, correlated well with the vaccine category used. Data generated by 85 experiments, which included vaccination of calves and guinea pigs with 18 reference vaccines of known potency, 8 placebos and 18 commercial vaccines, was subjected to statistical analysis. Concordance analysis indicated almost perfect agreement between the model and the target species for Ab titers measured by ELISA and almost perfect to substantial agreement when Ab titers were measured by VN. Taken together these results indicate that the developed guinea pig model represents a novel and reliable tool to estimate batch-to-batch vaccine potency and to predict efficacy of killed BoHV-1 veterinary vaccines.
牛传染性鼻气管炎（IBR）由牛疱疹病毒 1 型（BoHV-1）感染引起，分布于全球各地。BoHV-1 可单独或与其他呼吸道牛病原体一起导致畜牧业的重大经济损失。本工作的目的是验证豚鼠模型是否可替代当前针对犊牛的 BoHV-1 疫苗效力测试方法。豚鼠接受两剂疫苗免疫，间隔 21 天，于免疫后 30 天（dpv）采样。通过 ELISA 和病毒中和（VN）测定，比较了豚鼠接种疫苗后的 BoHV-1 抗体（Ab）反应与牛的 Ab 反应。豚鼠模型对疫苗中 BoVH-1 抗原浓度表现出剂量反应关系，并且能够区分疫苗中 BoHV-1 浓度相差 1log(10)的疫苗，具有很好的重复性和再现性（CV < 或 = 20%）。豚鼠和牛在 30 和 60 dpv 时获得的 Ab 滴度的回归分析允许我们将疫苗分为三种效力类别：“非常满意”、“满意”和“不满意”。用这些类别中的每一种疫苗免疫的牛均用 BoHV-1 病毒进行了攻毒实验，用病毒脱落量和疾病严重程度衡量的保护水平与使用的疫苗类别密切相关。通过对 85 项实验的数据进行统计分析，其中包括用 18 种参考疫苗（已知效力）、8 种安慰剂和 18 种商业疫苗免疫犊牛和豚鼠。协方差分析表明，ELISA 测定的 Ab 滴度模型与目标种属之间几乎完全一致，而 VN 测定的 Ab 滴度几乎完全一致至高度一致。综合这些结果表明，所建立的豚鼠模型代表了一种新颖而可靠的工具，可用于评估批间疫苗效力并预测灭活 BoHV-1 兽医疫苗的效力。
