The biological relevance of virus neutralisation sites for virulence and vaccine protection in the guinea pig model of foot-and-mouth disease

Abstract

Five neutralisation epitopes have been defined for the O1 Kaufbeuren strain of foot-and-mouth disease virus (FMDV) by neutralising murine monoclonal antibodies (Mabs). A mutant virus which is resistant to all these Mabs also resists neutralisation by bovine polyclonal sera, and this characteristic was exploited in the current study to investigate the biological relevance of neutralisation sites in FMDV virulence and vaccine protection. The five site neutralisation-resistant mutant was shown to be as pathogenic as wild-type virus in the guinea pig model of FMD. Guinea pigs were protected in cross-challenge studies from virulent wild-type and mutant viruses using either wild-type or mutant 146S antigen as inactivated whole virus vaccine. Furthermore, hyperimmune sera raised to either wild-type or mutant antigen offered passive protection against wild-type challenge, in spite of the serum raised against the mutant antigen having minimal neutralising activity in vitro. These results imply that virus neutralisation, at least as defined by the in vitro assay, may not play an essential role in the mechanism of immunity induced by whole inactivated FMDV vaccines.