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-infe...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 9; pp. 3286 - 3291
Main Authors:	Graham, S.P, Pelle, R, Honda, Y, Mwangi, D.M, Tonukari, N.J, Yamage, M, Glew, E.J, De Villiers, E.P, Shah, T, Bishop, R
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 28-02-2006 National Acad Sciences
Subjects:	Animals Antigens Antigens, Protozoan - immunology Biological Sciences Cattle CD8-positive T-lymphocytes Cell Line cell-mediated immunity clones Complementary DNA cytotoxic T-lymphocytes immune response Infections molecular sequence data nucleotide sequences Parasites Protozoan Vaccines - immunology Schizonts T lymphocytes T-Lymphocytes, Cytotoxic - immunology Theileria parva Theileria parva - immunology Theileriasis - immunology Theileriasis - parasitology Theileriasis - pathology Transponders Ungulates Vaccination vaccine development vaccines
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Summary:	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 naive 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 bPresent address: Department of Biochemistry, Delta State University, Abraka, Nigeria. Author contributions: S.P.G., R.P., Y.H., D.M.M., M.Y., C.M.F., I.M., M.J.G., S.P.M., S.C.G., J.-C.A., P.v.d.B., V.N., and E.L.N.T. designed research; S.P.G., R.P., Y.H., D.M.M., N.J.T., M.Y., E.J.G., E.P.d.V., T.S., R.B., E. Abuya, E. Awino, J.G., A.E.L., F.M., A.M.M., D.M.N., M.N., J.K.N., F.O.O., J.O., R.M.S., C.W., and S.L. performed research; R.B., S.L., S.C.G., and J.-C.A. contributed new reagents/analytic tools; S.P.G., R.P., Y.H., D.M.M., E.P.d.V., T.S., P.v.d.B., V.N., and E.L.N.T. analyzed data; and S.P.G., R.P., Y.H., D.M.M., M.J.G., P.v.d.B., V.N., and E.L.N.T. wrote the paper. cPresent address: Forensic Alliance Limited, Darwin House, Faraday Street, Birchwood Park, Risley, Warrington WA3 6AT, United Kingdom. jPresent address: Seattle Biomedical Research Institute, Suite 500, 307 Westlake Avenue N, Seattle, WA 98109. ePresent address: Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, Grafton, MA 01536. Communicated by Tilahun D. Yilma, University of California, Davis, CA, December 29, 2005 fPresent address: Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. dPresent address: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, P.O. Box 26901, 940 Stanton L. Young Boulevard, Biomedical Sciences Building, Room 853, Oklahoma City, OK 73190-0001. kPresent address: Food and Agriculture Organization, 39 Phra Atit Road, Bangkok 10200, Thailand.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0511273103