Abstract
BackgroundThe tick-borne protozoan parasite Theileria parva causes a usually fatal cattle disease known as East Coast fever in sub-Saharan Africa, with devastating consequences for poor small-holder farmers. Immunity to T. parva, believed to be mediated by a cytotoxic T lymphocyte (CTL) response, is induced following natural infection and after vaccination with a live vaccine, known as the Infection and Treatment Method (ITM). The most commonly used version of ITM is a combination of parasites derived from three isolates (Muguga, Kiambu 5 and Serengeti-transformed), known as the “Muguga cocktail”. The use of a vaccine comprising several strains is believed to be required to induce a broad immune response effective against field challenge. In this study we investigated whether immunization with the Muguga cocktail induces a broader CTL response than immunization with a single strain (Muguga).ResultsFour MHC haplotype-matched pairs of cattle were immunized with either the trivalent Muguga cocktail or the single Muguga strain. CTL specificity was assessed on a panel of five different strains, and clonal responses to these strains were also assessed in one of the MHC-matched pairs. We did not find evidence for a broader CTL response in animals immunized with the Muguga cocktail compared to those immunized with the Muguga strain alone, in either the bulk or clonal CTL analyses. This was supported by an in vivo trial in which all vaccinated animals survived challenge with a lethal dose of the Muguga cocktail vaccine stabilate.ConclusionWe did not observe any substantial differences in the immunity generated from animals immunized with either Muguga alone or the Muguga cocktail in the animals tested here, corroborating earlier results showing limited antigenic diversity in the Muguga cocktail. These results may warrant further field studies using single T. parva strains as future vaccine candidates.
Highlights
The tick-borne protozoan parasite Theileria parva causes a usually fatal cattle disease known as East Coast fever in sub-Saharan Africa, with devastating consequences for poor small-holder farmers
Eight Bos taurus cattle were bought from farms in the Nyeri area in Kenya. They were screened free for tickborne diseases including T. parva, and BoLA typed using a combination of serology (ELISA using antibodies defining particular Major Histocompatibility Complex (MHC) haplotypes), Interferon Gamma (IFNγ) ELISPOT assay using Peripheral Blood Mononuclear Cells (PBMC) from the cattle pulsed with Tp1214–224 and a peptide-specific cytotoxic T lymphocyte (CTL) line, and by PCR using haplotype specific primers followed by sequencing, essentially as described before [25]
CTL were generated from all animals and tested against autologous cell lines infected with five cloned sporozoite stabilates and an MHC-mismatched infected cell line as control
Summary
The tick-borne protozoan parasite Theileria parva causes a usually fatal cattle disease known as East Coast fever in sub-Saharan Africa, with devastating consequences for poor small-holder farmers. Immunity to T. parva, believed to be mediated by a cytotoxic T lymphocyte (CTL) response, is induced following natural infection and after vaccination with a live vaccine, known as the Infection and Treatment Method (ITM). Theileria parva is a tick-borne protozoan parasite which causes an acute and usually fatal cattle disease, known as East Coast fever, in eastern, central and southern Africa. The parasite infects bovine lymphocytes, which subsequently undergo blast transformation and rapid multiplication [1] In susceptible animals, this usually results in overwhelming parasitosis and death within 2 to 4 weeks of infection. Cattle which recover from natural infection can develop a strong immunity to subsequent challenge This has been exploited to develop a vaccination procedure known as the “Infection and Treatment Method” (ITM) in which live sporozoites are administered simultaneously with oxytetracycline. It has been shown that the time point of recovery correlates with a peak of CD8+ cells in the blood of the infected animals [3]
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