Development of a Potential Yeast-Based Vaccine Platform for Theileria parva Infection in Cattle
East Coast Fever (ECF), caused by the tick-borne apicomplexan parasite Theileria 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 Meth...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.674484/full |
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| author | Shan Goh Jeannine Kolakowski Angela Holder Mark Pfuhl Daniel Ngugi Keith Ballingall Kata Tombacz Dirk Werling |
| author_facet | Shan Goh Jeannine Kolakowski Angela Holder Mark Pfuhl Daniel Ngugi Keith Ballingall Kata Tombacz Dirk Werling |
| author_sort | Shan Goh |
| collection | DOAJ |
| description | East Coast Fever (ECF), caused by the tick-borne apicomplexan parasite Theileria 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 different T. parva schizont antigens (Tp1, Tp2, Tp9, Tp10 and N36) and Saccharomyces cerevisiae as an expression platform. Full-length Tp2 and Tp9 as well as fragments of Tp1 were successfully expressed on the surface of S. cerevisiae. In vitro analyses 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 subsequent in vivo study 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. |
| first_indexed | 2024-12-19T05:51:41Z |
| format | Article |
| id | doaj.art-aa7c9e5d52604a3780387d499f3bdf02 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T05:51:41Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aa7c9e5d52604a3780387d499f3bdf022022-12-21T20:33:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.674484674484Development of a Potential Yeast-Based Vaccine Platform for Theileria parva Infection in CattleShan Goh0Jeannine Kolakowski1Angela Holder2Mark Pfuhl3Daniel Ngugi4Keith Ballingall5Kata Tombacz6Dirk Werling7Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, United KingdomDepartment of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, United KingdomDepartment of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, United KingdomFaculty of Life Science and Medicine, King’s College London, London, United KingdomDepartment of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, United KingdomMoredun Research Institute, Penicuik, United KingdomDepartment of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, United KingdomDepartment of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, United KingdomEast Coast Fever (ECF), caused by the tick-borne apicomplexan parasite Theileria 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 different T. parva schizont antigens (Tp1, Tp2, Tp9, Tp10 and N36) and Saccharomyces cerevisiae as an expression platform. Full-length Tp2 and Tp9 as well as fragments of Tp1 were successfully expressed on the surface of S. cerevisiae. In vitro analyses 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 subsequent in vivo study 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.674484/fullTheileria parvaEast Coast Feverschizont antigensoral vaccineyeast |
| spellingShingle | Shan Goh Jeannine Kolakowski Angela Holder Mark Pfuhl Daniel Ngugi Keith Ballingall Kata Tombacz Dirk Werling Development of a Potential Yeast-Based Vaccine Platform for Theileria parva Infection in Cattle Frontiers in Immunology Theileria parva East Coast Fever schizont antigens oral vaccine yeast |
| title | Development of a Potential Yeast-Based Vaccine Platform for Theileria parva Infection in Cattle |
| title_full | Development of a Potential Yeast-Based Vaccine Platform for Theileria parva Infection in Cattle |
| title_fullStr | Development of a Potential Yeast-Based Vaccine Platform for Theileria parva Infection in Cattle |
| title_full_unstemmed | Development of a Potential Yeast-Based Vaccine Platform for Theileria parva Infection in Cattle |
| title_short | Development of a Potential Yeast-Based Vaccine Platform for Theileria parva Infection in Cattle |
| title_sort | development of a potential yeast based vaccine platform for theileria parva infection in cattle |
| topic | Theileria parva East Coast Fever schizont antigens oral vaccine yeast |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.674484/full |
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