Characterisation of loci that encode immunoprotective antigens of Eimeria maxima identified through genetic linkage analysis

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

The eimerian genome has been estimated to encode 6,000-8,000 gene products based upon comparison with the sequenced genomes of related apicomplexan parasites. To date, the absence of a rational approach to distinguish genuinely immunoprotective antigens from those that are immunogenic, but non-protective, has seriously hampered the identification of antigens suitable for inclusion in recombinant vaccines protective against Eimeria species. Our recent development of a classical genetic mapping strategy based upon uncloned populations (comparable with hitchhiker mapping) has allowed us to map regions of the Eimeria maxima genome eliminated from a hybrid parasite population under strain-specific immune selection. Three distinct clusters of physically linked AFLP markers specific to the E. maxima strain under immune selection have been identified. Each cluster covers a region of approximately 100-230 Kb in the approximately 60 Mb genome. We propose to sequence a panel of BAC clones covering these regions and predict the genes encoded using software developed and trained for annotation of the Eimeria tenella genome sequencing project. Those genes located in regions subject to immune selection (detected by the loss of parent- specific AFLP markers) that are polymorphic between antigenically distinct parents at the amino acid level will be surveyed for the ability to induce CD4+ T cell proliferation and interferon-gamma mRNA expression (mechanisms known to be stimulated by natural eimerian infection) and stimulate a protective immune response in the host. Up to ten candidate genes will be subjected to testing in vaccination trials.

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