Evidence that use of an inactivated equine herpesvirus vaccine induces serum cytotoxicity affecting the equine arteritis virus neutralisation test

Several laboratories worldwide have recently experienced problems related to serum cytotoxicity with the equine arteritis virus (EAV) neutralisation test (VN) when using Office International des Epizooties (OIE) reference laboratory prescribed rabbit kidney (RK-13) indicator cells. Cytotoxicity can be mistaken for viral cytopathic effect and has led to increasing difficulties in test interpretation, consequently causing disruption to both equine breeding and disease surveillance. Results from experimental and field-derived data suggest that this serum cytotoxicity is associated with use of a tissue-culture-derived equine herpesvirus vaccine, probably manifested through a vaccine-induced anti-cellular antibody response directed against RK-13 cells. Two alternative EAV VN methods were shown to significantly reduce the effects of cytotoxicity (from 73 to <5% prevalence) among vaccinated horses but did not completely eliminate the problem. Use of ELISA-based tests, which are not affected by serum cytotoxicity but which are not currently recognised as international standards, should be evaluated as a useful backup in screening equine sera for EAV VN antibodies.