THEILERIOSIS - PROGRESS TOWARDS VACCINE DEVELOPMENT THROUGH UNDERSTANDING IMMUNE-RESPONSES TO THE PARASITE

Studies of the immune responses of cattle to Theileria parva have prov ided evidence that immunity to the parasite can operate at two levels, namely the sporozoite and the schizont-infected lymphoblast. Antibodi es that neutralize the infectivity of sporozoites have been detected i n the serum of hyperimmunized cattle, and a recombinant sporozoite sur face antigen has been shown to induce neutralizing antibodies and prot ection against experimental challenge. However, the immunity that deve lops following primary infection with T. parva is accompanied by only low levels of antibodies to sporozoites; there is overwhelming evidenc e that under these circumstances protection is mediated by T cell resp onses against infected lymphoblasts. Potent class I MHC-restricted cyt otoxic T lymphocyte (CTL) responses are detected in animals recovering from infection and treatment or challenge infections. Two recent find ings have provided direct evidence for the importance of these respons es in immunity. First, the strain specificity of CTL in cattle immuniz ed with one stock of the parasite was found to correlate with the subs equent susceptibility of individual animals to challenge with a hetero logous cloned parasite population (in these circumstances some animals are protected whereas others are susceptible to the heterologous chal lenge). Second, the adoptive transfer of lymphocytes highly enriched f or CD8(+) T cells, from immune to naive identical twin calves, was fou nd to protect against experimental challenge. The CTL response in indi vidual animals appears to be directed towards a limited number of anti genic epitopes. The antigenic specificity is determined in part by cla ss I MHC phenotype although there is evidence that other phenomena suc h as antigenic competition are also involved. Current efforts are dire cted towards identification of the parasite antigens recognized by CTL with the eventual aim of exploring their potential for vaccination.