Emerging foot-and-mouth disease virus variants with antigenically critical amino acid substitutions predicted by model studies using reference viruses.

One of the major obstacles to the design of effective antiviral vaccines is the frequent generation of antigenic viral variants in the field. The types of variants that will become dominant during disease outbreaks is often unpredictable. However, here we report the genetic and antigenic characterization of emerging foot-and-mouth disease virus (FMDV) variants with antigenically critical amino acid substitutions predicted by model studies using reference viruses and monoclonal antibodies. The new variants belong to serotype C and have caused a number of recent disease outbreaks in Argentina. The variants harbor antigenically drastic amino acid substitutions in each of the antigenic sites identified in FMDV. In particular, a substitution found at a major antigenic site (site A, the G-H loop of VP1) had been repeatedly selected in viruses resistant to neutralization by monoclonal and polyclonal antibodies. The association of critical amino acid replacements at predicted positions with new FMD outbreaks has a number of implications for FMD epidemiology and for the design of vaccines intended to control diseases caused by highly variable RNA viruses.