Differential antibody responses to the major antigenic sites of FMD virus serotype O after primo-vaccination, multiply-vaccination and after natural exposure

Foot and mouth disease (FMD) virus serotype O is the predominant cause of FMD outbreaks in several regions of the world including India. Five independent neutralizing antigenic sites have been identified on the capsid surface of FMD virus serotype O. The relative importance of these neutralizing sites in eliciting antibody responses in the polyclonal sera collected from un-infected vaccinated (both primo and multiply-vaccinated) and naturally infected cattle populations were determined through a combination of reverse genetics and serology. The known critical amino acid residues present on the five antigenic sites of FMD virus serotype O Indian vaccine strain O IND R2/1975 were mutated through site-directed mutagenesis. The mutant viruses were rescued in cell-culture and analyzed through virus-neutralization assays along with parent virus using the polyclonal sera collected from three groups of cattle. In the polyclonal sera from primo-vaccinated cattle, significantly higher level of antibodies were directed towards antigenic site 2. In contrast, in polyclonal sera from multiply vaccinated animals, both antigenic sites 1 and 2 were equally important. In case of naturally infected animals, antibody responses were elicited against all the five antigenic sites. Although a drop in neutralization titres was observed for all the mutants, in one instance, increase in titre was noticed for a site 3 mutant. The findings from this study extend our knowledge on the antibody immunodominace following FMDV vaccination and infection, and may improve our strategies for vaccine strain selection and rational vaccine design.