P. Zamorano et al., 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, Virology, 212(2), 1995, pp. 614-621
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.