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口蹄疫疫苗的效力测试小鼠模型。

Mouse model as an efficacy test for foot-and-mouth disease vaccines.

机构信息

Instituto Nacional de Tecnología Agropecuaria, Nicolas Repetto y Los Reseros, Buenos Aires, Argentina.

出版信息

Transbound Emerg Dis. 2020 Nov;67(6):2507-2520. doi: 10.1111/tbed.13591. Epub 2020 May 15.

DOI:10.1111/tbed.13591
PMID:32320534
Abstract

Protection against foot-and-mouth disease virus (FMDV) has been linked to the development of a humoral response. In Argentina, the official control tests for assessing the potency of FMD vaccines are protection against podal generalization (PPG) and expected percentage of protection (EPP) curves built with quantitative data of antibodies determined by liquid-phase blocking ELISA (lpELISA). The results of these tests are used to accept or discard vaccines at the batch level. In this report, a mouse model was assessed as an alternative efficacy control for FMDV vaccines. To this aim, groups of cattle (n = 18) and BALB/c mice (n = 16) were inoculated with commercial FMDV vaccines and bleedings were performed 60 days post vaccination (dpv) in cattle and 21 dpv in mice. Specific FMDV antibody titres were measured in both species by a standardized lpELISA. A statistically significant association between antibody levels in cattle and mice has already been demonstrated. However, some vaccines have been misclassified since they were considered protective based on lpELISA results but did not induce good protection in cattle upon challenge. For this reason, other immunological parameters were evaluated to improve the prediction of protection in mice, without the need of using infective virus. In addition, antibody titres by lpELISA, the IgG2b/IgG1 isotype ratio and the Avidity Index were identified as good predictors, resulting in an optimal predictive model of protection. This mouse model could be a simple and economic alternative for testing FMD vaccines since the disadvantages of high costs and facility requirements associated with the use of large animals are overcome.

摘要

针对口蹄疫病毒(FMDV)的保护作用与体液免疫反应的发展有关。在阿根廷,评估 FMD 疫苗效力的官方控制测试是针对足部泛化(PPG)和预期保护率(EPP)的曲线,这些曲线是通过液相阻断 ELISA(lpELISA)定量测定的抗体数据构建的。这些测试的结果用于在批次水平上接受或淘汰疫苗。在本报告中,评估了小鼠模型作为 FMDV 疫苗的替代功效控制方法。为此,将牛(n=18)和 BALB/c 小鼠(n=16)分组接种商业 FMDV 疫苗,并在牛接种后 60 天(dpv)和小鼠 21 天(dpv)采血。通过标准化的 lpELISA 测量两种动物的特定 FMDV 抗体滴度。已经证明牛和小鼠之间的抗体水平存在统计学显著相关性。然而,一些疫苗被错误分类,因为根据 lpELISA 结果,它们被认为是有保护作用的,但在接种后不能在牛中诱导良好的保护作用。因此,评估了其他免疫参数,以提高对小鼠保护作用的预测,而无需使用感染性病毒。此外,lpELISA 抗体滴度、IgG2b/IgG1 同型比值和亲和指数被确定为良好的预测因子,从而得出了保护作用的最佳预测模型。这种小鼠模型可以作为测试 FMD 疫苗的简单而经济的替代方法,因为它克服了使用大型动物相关的高成本和设施要求的缺点。

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