Location: Animal Disease Research
Project Number: 2090-32000-039-029-A
Project Type: Cooperative Agreement
Start Date: Jan 1, 2019
End Date: Dec 31, 2020
Objective:
East Coast Fever (ECF), caused by Theileria parva, kills over one million cattle in sub-Saharan Africa each year , resulting in extreme financial hardship and food shortages for smallholder farmers. As an intracellular parasite, immune control of ECF is largely dependent upon the development a robust, MHC class I-restricted CD8+ T-lymphocyte response . The development of a vaccine for ECF is imperative; however, due to the complexity of antigen processing and presentation in outbred species, and the antigenic complexity of the parasite, all next generation vaccines tested to date have failed to reproduce premonition. The objective of this study is to test the hypothesis that immunization of cattle with a minigene library of selected T. parva genes provides protective immune responses against Theileria parva.
Approach:
A library of full-length and minigene T. parva antigens will be generated, and DNA-encoded antigens attached to microscopic gold beads for use in gene-gun immunization. Six MHC class I-genotype matched cattle will be gene-gun immunized with the library of full-length and minigene T. parva antigens. Two MHC class-I cattle will be sham-immunized as negative controls. The immunization schedule will consist of one priming immunization followed by two or more booster immunizations spaced at least 30 days apart. Beginning one month after the first immunization, serum and white blood cells will be collected every 2-4 weeks from immunized cattle and assessed for immune-responsiveness to T. parva using a battery of in vitro assays, including ELISA, interferon gamma ELISPOT, and flow cytometry. Once cattle develop an immune response, they will be challenged with a lethal dose of T. parva, and protection from disease assessed clinically.
