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      Exposure of vaccinated and naive cattle to natural challenge from buffalo-derived Theileria parva

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          Highlights

          • The Muguga cocktail was tested in cattle in a buffalo-only location.

          • Infection with buffalo-derived T. parva caused Corridor disease in cattle.

          • At the conservancy, the cocktail did not protect cattle against Corridor disease.

          • Efficacious vaccines can support integrative livestock/wildlife management.

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          Abstract

          Integrative management of wildlife and livestock requires a clear understanding of the diseases transmitted between the two populations. The tick-borne protozoan parasite Theileria parva causes two distinct diseases in cattle, East Coast fever and Corridor disease, following infection with parasites derived from cattle or buffalo, respectively. In this study, cattle were immunized with a live sporozoite vaccine containing three T. parva isolates (the Muguga cocktail), which has been used extensively and successfully in the field to protect against cattle-derived T. parva infection. The cattle were exposed in a natural field challenge site containing buffalo but no other cattle. The vaccine had no effect on the survival outcome in vaccinated animals compared to unvaccinated controls: nine out of the 12 cattle in each group succumbed to T. parva infection. The vaccine also had no effect on the clinical course of the disease. A combination of clinical and post mortem observations and laboratory analyses confirmed that the animals died of Corridor disease. The results clearly indicate that the Muguga cocktail vaccine does not provide protection against buffalo-derived T. parva at this site and highlight the need to evaluate the impact of the composition of challenge T. parva populations on vaccine success in areas where buffalo and cattle are present.

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          Most cited references28

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          Theileria parva candidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes.

          East Coast fever, caused by the tick-borne intracellular apicomplexan parasite Theileria parva, is a highly fatal lymphoproliferative disease of cattle. The pathogenic schizont-induced lymphocyte transformation is a unique cancer-like condition that is reversible with parasite removal. Schizont-infected cell-directed CD8(+) cytotoxic T lymphocytes (CTL) constitute the dominant protective bovine immune response after a single exposure to infection. However, the schizont antigens targeted by T. parva-specific CTL are undefined. Here we show the identification of five candidate vaccine antigens that are the targets of MHC class I-restricted CD8(+) CTL from immune cattle. CD8(+) T cell responses to these antigens were boosted in T. parva-immune cattle resolving a challenge infection and, when used to immunize naïve cattle, induced CTL responses that significantly correlated with survival from a lethal parasite challenge. These data provide a basis for developing a CTL-targeted anti-East Coast fever subunit vaccine. In addition, orthologs of these antigens may be vaccine targets for other apicomplexan parasites.
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            An enzyme-linked immunosorbent assay for detection of Theileria parva antibodies in cattle using a recombinant polymorphic immunodominant molecule.

            Field and experimental bovine infection sera were used in immunoblots of sporozoite and schizont lysates of Theileria parva to identify candidate diagnostic antigens. Four parasite antigens of Mr 67,000 (p67), 85,000 (the polymorphic immunodominant molecule, PIM), 104,000 (p104), and 150,000 (p150) were selected for a more detailed analysis. The p67 and p104 antigens were present only in the sporozoite lysates, whereas PIM and p150 were found in both sporozoite and schizont lysates. The four antigens were expressed as recombinant fusion proteins and were compared with each other in an enzyme-linked immunosorbent assay (ELISA) and in the whole-schizont-based indirect fluorescent antibody test (IFAT) in terms of their ability to detect antibodies in sera of experimentally infected cattle. The PIM-based ELISA provided a higher degree of sensitivity and specificity than did the ELISA using the other three recombinant antigens or the IFAT. Further evaluation of the PIM-ELISA using experimental sera derived from cattle infected with different hemoparasites and field sera from endemic and nonendemic T. parva areas showed that the assay had a sensitivity of > 99% and a specificity of between 94% and 98%.
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              Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

              Background Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8+ T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8+ T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8+ T-cell epitopes, and to analyse the sequences for evidence of selection. Methodology/Principal Findings Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (∼12%) in Tp1 and in 320 positions (∼61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle. Conclusions/Significance The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.
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                Author and article information

                Contributors
                Journal
                Int J Parasitol Parasites Wildl
                Int J Parasitol Parasites Wildl
                International Journal for Parasitology: Parasites and Wildlife
                Elsevier
                2213-2244
                08 May 2015
                August 2015
                08 May 2015
                : 4
                : 2
                : 244-251
                Affiliations
                [a ]International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi 00100, Kenya
                [b ]Ol Pejeta Conservancy, Private Bag, Nanyuki 10400, Kenya
                [c ]Veterinary Services Department, Kenya Wildlife Service, P.O. Box 40241-00100, Nairobi, Kenya
                [d ]The Roslin Institute, The University of Edinburgh, Midlothian EH25 9RG, UK
                Author notes
                [* ]Corresponding author. University of Vermont, Department of Animal and Veterinary Science, 570 Main Street, 311 Terrill Bldg., Burlington, VT 05405, USA. Tel.: + 9255494032; fax: +1-802-656-8196. tsitt@ 123456uvm.edu
                [** ]Corresponding author. International Livestock Research Institute (ILRI), P.O. Box 30709, Nairobi 00100, Kenya. Tel.: +254 20 422 3643. p.toye@ 123456cgiar.org
                [1]

                Present address: Department of Animal and Veterinary Science, University of Vermont, 570 Main Street, 311 Terrill Bldg., Burlington, VT 05405, USA.

                Article
                S2213-2244(15)00022-X
                10.1016/j.ijppaw.2015.04.006
                4437466
                26005635
                6abc8747-7725-4cb3-adac-4eeb78104eda
                © 2015 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 17 March 2015
                : 29 April 2015
                : 30 April 2015
                Categories
                Article

                theileria parva,cattle,buffalo,vaccine,sporozoite,muguga cocktail

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