Accuracy of traditional and novel serology tests for predicting cross-protection in foot-and-mouth disease vaccinated cattle

Foot-and-mouth disease virus (FMDV) antigenic-match between vaccine and field viruses has traditionally been estimated in vitro by computing the r1 value using virus neutralization test (VNT) or ELISA titers. In this study we compared the accuracy in predicting cross-protection between the r1 value estimated by VNT and two recently developed tests that measure IgG subtypes and avidity. Data analyzed consisted of 64 serum samples from FMDV A24/Cruzeiro vaccinated bovines challenged with the heterologous A/Argentina/2001 strain and evaluated for podal generalization. We computed the tests sensitivity (Se), specificity (Sp), and receiving operating characteristics (ROC) curve. The heterologous IgG1/IgG2 ratio was the most accurate test (Se. = 0.71, Sp. = 0.98), followed by heterologous IgG1 (Se. = 0.53, Sp. = 0.96), VNT (Se. = 0.47, Sp. = 1.00), whereas r1 accuracy was substantially low (Se. = 0.41, Sp. = 0.81). Because sensitivity of individual tests was limited, we argue that two or more of the tests should be used in combination to produce accurate estimates of protection.