Development of a potential yeast-based vaccine platform for Theileria parva infection in cattle
East Coast Fever (ECF), caused by the tick-borne apicomplexan parasiteTheileria parva, remains one of the most important livestock diseases in sub-Saharan Africa with more than 1 million cattle dying from infection every year. Disease prevention relies on the so-called “Infection and Treatment Method” (ITM), which is costly, complex, laborious, difficult to standardise on a commercial scale and results in a parasite strain-specific, MHC class I-restricted cytotoxic T cell response. We therefore attempted to develop a safe, affordable, stable, orally applicable and potent subunit vaccine for ECF using five differentT. parvaschizont antigens (Tp1, Tp2, Tp9, Tp10 and N36) andSaccharomyces cerevisiaeas an expression platform. Full-length Tp2 and Tp9 as well as fragments of Tp1 were successfully expressed on the surface ofS. cerevisiae.In vitroanalyses highlighted that recombinant yeast expressing Tp2 can elicit IFNγ responses using PBMCs from ITM-immunized calves, while Tp2 and Tp9 induced IFNγ responses from enriched bovine CD8+T cells. A subsequentin vivostudy showed that oral administration of heat-inactivated, freeze-dried yeast stably expressing Tp2 increased total murine serum IgG over time, but more importantly, induced Tp2-specific serum IgG antibodies in individual mice compared to the control group. While these results will require subsequent experiments to verify induction of protection in neonatal calves, our data indicates that oral application of yeast expressing Theileria antigens could provide an affordable and easy vaccination platform for sub-Saharan Africa. Evaluation of antigen-specific cellular immune responses, especially cytotoxic CD8+T cell immunity in cattle will further contribute to the development of a yeast-based vaccine for ECF.
| Main Authors: | , , , , , , , |
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| Format: | Journal Article biblioteca |
| Language: | English |
| Published: |
Frontiers Media
2021-07-08
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| Subjects: | theileria parva, animal diseases, east coast fever, disease control, cattle, livestock, vaccines, |
| Online Access: | https://hdl.handle.net/10568/114269 https://doi.org/10.3389/fimmu.2021.674484 |
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| Summary: | East Coast Fever (ECF), caused by the tick-borne apicomplexan parasiteTheileria parva, remains one of the most important livestock diseases in sub-Saharan Africa with more than 1 million cattle dying from infection every year. Disease prevention relies on the so-called “Infection and Treatment Method” (ITM), which is costly, complex, laborious, difficult to standardise on a commercial scale and results in a parasite strain-specific, MHC class I-restricted cytotoxic T cell response. We therefore attempted to develop a safe, affordable, stable, orally applicable and potent subunit vaccine for ECF using five differentT. parvaschizont antigens (Tp1, Tp2, Tp9, Tp10 and N36) andSaccharomyces cerevisiaeas an expression platform. Full-length Tp2 and Tp9 as well as fragments of Tp1 were successfully expressed on the surface ofS. cerevisiae.In vitroanalyses highlighted that recombinant yeast expressing Tp2 can elicit IFNγ responses using PBMCs from ITM-immunized calves, while Tp2 and Tp9 induced IFNγ responses from enriched bovine CD8+T cells. A subsequentin vivostudy showed that oral administration of heat-inactivated, freeze-dried yeast stably expressing Tp2 increased total murine serum IgG over time, but more importantly, induced Tp2-specific serum IgG antibodies in individual mice compared to the control group. While these results will require subsequent experiments to verify induction of protection in neonatal calves, our data indicates that oral application of yeast expressing Theileria antigens could provide an affordable and easy vaccination platform for sub-Saharan Africa. Evaluation of antigen-specific cellular immune responses, especially cytotoxic CD8+T cell immunity in cattle will further contribute to the development of a yeast-based vaccine for ECF. |
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