Veterinary Science - Theses
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ItemCharacterization of the eg95 gene family in Echinococcus granulosus G6 genotype: implications for the efficacy of the EG95 vaccine against genotypes other than G1( 2011)Cystic echinococcosis (CE) in humans and livestock animals is caused by infection with the cestode parasite Echinococcus granulosus. The parasite has a worldwide distribution, causing human morbidity and mortality as well as economic losses. E. granulosus presents significant intraspecific variability and several different genotypes have been described varying with respect to host preference and other biological characteristics. The G1 genotype is the variant most commonly associated with human infections worldwide, with genotype G6 also causing a significant proportion of human CE cases. A recombinant vaccine, designated EG95, has been developed for use in animals to interrupt the cycle of transmission of E. granulosus, with a view to decreasing the transmission of the parasite to humans. The vaccine is based on an antigen expressed in the oncosphere of E. granulosus. EG95 is encoded by members of a family of closely related genes in the G1 genotype. Potential variability in the protein target of the EG95 vaccine in different genotypes of E. granulosus could lead to parasites of genotypes other than G1 being insusceptible to the vaccine. Currently there is no reliable information about the likely efficacy of the EG95 vaccine against genotypes other than G1. The principal aim of the research described in this thesis was to provide information about the variability of the eg95-related gene(s) and their predicted protein products in the G6 genotype of E. granulosus, and other genotypes, also providing data that could be used for assessment of the antigenicity of the EG95-related proteins in each genotype. Using genomic DNA cloning techniques, seven members of an eg95 –related gene family were characterised from the G6 genotype of E. granulosus. Three proteins are predicted to be encoded by these genes, with two genes considered to be pseudogenes. Investigations were undertaken to determine the ability of two of theEG95-related proteins, encoded by genes in the G6 genotype, to react with specific antibodies in the sera of sheep vaccinated with EG95 and shown to be protected against a challenge infection with the G1 genotype. Proteins encoded by genes in the G6 genotype displayed only limited antigenic cross-reactivity with the current EG95 vaccine antigen, suggesting that the current vaccine may not protect animals against an infection with parasites of the G6 genotype. Data presented in this thesis provides the information that would enable a G6 genotype-specific vaccine to be developed against E. granulosus, should this be considered a desirable addition to the available tools for control of CE transmission.