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

Author:
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.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2006 v.103 no.9 pp. 3286-3291
ISSN:
0027-8424
Subject:
cattle, cytotoxic T-lymphocytes, CD8-positive T-lymphocytes, immune response, cell-mediated immunity, antigens, Theileria parva, vaccines, vaccine development, schizonts, complementary DNA, clones, nucleotide sequences
Abstract:
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.
Agid:
2350631