Foot-and-mouth disease virus non-structural protein antibody detection: from DIVA serology to repeated-epitope design and multi-species field surveillance

Surveillance for foot-and-mouth disease (FMD) in vaccinated populations requires tests that distinguish vaccine-induced immunity from infection-associated exposure. Structural protein antibodies help assess vaccine response and serotype-specific protection, whereas antibodies to foot-and-mouth disease virus (FMDV) non-structural proteins (NSPs) support DIVA (differentiating infected from vaccinated animals) interpretation only when vaccine purity and vaccination history are considered. Residual NSPs in incompletely purified vaccines, repeated vaccination, antibody kinetics, host species and assay cut-offs all influence interpretation. This Mini Review examines NSP antibody detection based on 3ABC, 3B/VPg repeated-epitope design, complementary NSP targets, competitive or blocking ELISA, multi-species-compatible assays and emerging field-deployable formats. It does not rank platforms as universally superior; instead, it considers reported performance, validation context and field setting. NSP serology is most useful when combined with vaccination records, structural protein serology, RT-qPCR and epidemiological investigation. It can flag possible subclinical exposure or post-outbreak risk, but it is not a standalone test for current shedding, persistent infection or carrier status.