Neutralization Sites of Type O1 Foot-and-mouth Disease Virus Defined by Monoclonal Antibodies and Neutralization-escape Virus Variants

Monoclonal antibodies (MAbs) were derived from mice infected with foot-and-mouth disease virus type O1 Brugge (FMDV 01B) or immunized with inactivated virions (140 S) or viral subunits (12 S). A total of 19 neutralizing MAbs were characterized of which 17 recognized conformationally determined epitopes and two recognized amino acid sequences on isolated VP1. Neutralizing MAbs were used to select antigenic variants of FMDV O1B. Based on cross-neutralization and binding assays with MAbs the variants were divided into discrete groups demonstrating the presence of three unique neutralization sites on FMDV O1B. One site was present only on intact 140 S virions, a second was present on both 140 S virions and 12 S subunits, and the third was present on 140 S virions, 12 S subunits, and isolated VP1. Comparison of the deduced nucleic acid sequence of parental FMDV O1B with those of the O1B variants demonstrated that the epitope recognized by the VP1-reactive, neutralizing MAbs included amino acid residues 138, 144, and 148. Cross-neutralization assays demonstrated that these neutralization sites of FMDV O1B function on other type O1 strains of FMDV.