A LARGE-SCALE EVALUATION OF PEPTIDE VACCINES AGAINST FOOT-AND-MOUTH-DISEASE - LACK OF SOLID PROTECTION IN CATTLE AND ISOLATION OF ESCAPE MUTANTS

A large-scale vaccination experiment involving a total of 138 cattle w as carried out to evaluate the potential of synthetic peptides as vacc ines against foot-and-mouth disease. Four types of peptides representi ng sequences of foot and mouth disease virus (FMDV) C3 Argentina 85 we re tested: A, which includes the G-H loop of capsid protein VP1 (site ri); AT, in which a T-cell epitope has been added to site A; AC, compo sed of site A and the carboxy-terminal region of VP1 (site C); and ACT , in which the three previous capsid motifs are colinearly represented . Induction of neutralizing antibodies, lymphoproliferation in respons e to viral antigens, and protection against challenge with homologous infectious virus were examined. None of the tested peptides, at severa l doses and vaccination schedules, afforded protection above 40%. Prot ection showed limited correlation with serum neutralization activity a nd lymphoproliferation in response to whole virus. In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mu tant FMDVs with amino acid substitutions at antigenic site A were iden tified. This finding suggests the rapid generation and selection of FM DV antigenic variants in vivo. In contrast with previous studies, this large-scale vaccination experiment with an important FMDV host reveal s considerable difficulties for vaccines based on synthetic peptides t o achieve the required levels of efficacy. Possible modifications of t he vaccine formulations to increase protective activity are discussed.