A 10-AMINO-ACID LINEAR SEQUENCE OF VP1 OF FOOT-AND-MOUTH-DISEASE VIRUS CONTAINING B-CELL AND T-CELL EPITOPES INDUCES PROTECTION IN MICE

The area of foot and mouth disease virus (FMDV) comprising residues 14 0 and 160 of capsid protein VP1 has been used extensively as an immuno gen in natural and experimental hosts. A detailed epitope mapping of t his region, however, has not been reported. For this purpose a synthet ic peptide containing the residues 135 to 160 (p135-160) of VP1 of FMD V O-1 Campos was analyzed for its T- and B-cell epitopes. The p135-160 is highly immunogenic, either by itself or coupled to a carrier prote in (BsA), elicits a long-lasting neutralizing antibody response in mic e, and provides solid protection against virulent challenge. By using a set of synthetic 10mer overlapping peptides, which cover the entire sequence 135-160 of VP1, we have shown that at least four discrete B e pitopes are regularly distributed along the peptide. Although immuniza tion with each of the 10mers coupled with BSA as a carrier protein ind uced peptide-specific antibody responses, individually none of the 10m ers was able to induce neutralizing antibodies. However, anti-135-160 antibodies sorted by immunoaffinity chromatography using each of the 1 0mers revealed the existence of at least four discrete neutralizing si tes: one spanning residues 135-144, at least two more between residues 140 and 154, and another in the region 150-160. Moreover, T-cell epit opes were identified, both by antigen-dependent proliferation assays a nd by adoptive cell transfer. By both methods, a T-cell epitope was lo cated in the area comprising residues 135-144; the cell transfer exper iment, which seems to be more sensitive, also identified a second T-ce ll epitope between residues 150 and 160. Interestingly, when the regio n 135-144, which contains both B- and T-cell epitopes, was in a tandem repeat configuration it induced a strong neutralizing antibody respon se in mice and solid protection against the challenge. (C) 1995 Academ ic Press, Inc.