Linear peptide specificity of bovine antibody responses to p67 of Theileria parva and sequence diversity of sporozoite-neutralizing epitopes: Implications for a vaccine

A stage-specific surface antigen of Theileria parva, p67, is the basis for the development of an anti-sporozoite vaccine for the control of East Coast fever (ECF) in cattle. By Pepscan analysis with a series of overlapping sy nthetic p67 peptides, the antigen was shown to contain five distinct linear peptide sequences recognized by sporozoite-neutralizing murine monoclonal antibodies. Three epitopes were located between amino acid positions 105 to 229 and two were located between positions 617 to 639 on p67, Bovine antib odies to a synthetic peptide containing one of these epitopes neutralized s porozoites, validating this approach for defining immune responses that are likely to contribute to immunity. Comparison of the peptide specificity of antibodies from cattle inoculated with recombinant p67 that were immune or susceptible to ECF did not reveal statistically significant differences be tween the two groups. In general, antipeptide antibody levels in the suscep tible animals were lower than in the immune group and neither group develop ed high responses to all sporozoite-neutralizing epitopes, The bovine antib ody response to recombinant p67 was restricted to the N- and C-terminal reg ions of p67, and there was no activity against the central portion between positions 313 and 583. So far, p67 sequence polymorphisms have been identif ied only in buffalo-derived T, pan a parasites, but the consequence of thes e for vaccine development remains to be defined. The data indicate that opt imizations of the current vaccination protocol against ECF should include b oosting of relevant antibody responses to neutralizing epitopes on p67.