Understanding the basis of strain restricted immunity to Theileria parva

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Over 20% of people in sub-Saharan Africa are classified as living below the poverty line and many of these people reside in rural communities that are heavily dependent on livestock for their livelihoods. Infectious diseases have a major impact on livestock production in these regions. One of the most important diseases of cattle is East Coast fever (ECF) caused by a tick-borne parasite Theileria parva. This disease is present in 16 countries in eastern and southern Africa and it is the most economically important cattle disease in 11 of these countries. Estimates of economic losses due to ECF exceed 300 million US dollars annually. Imported breeds of cattle, which are increasingly being used to satisfy demands for milk production, are particularly susceptible. Although treatment of infected animals with anti-parasitic drugs and application of chemicals to prevent tick infestation can be used to control ECF, these methods are difficult to apply and generally are unaffordable by poor livestock keepers. Vaccination, therefore offers a more sustainable means of controlling the disease. Cattle can be immunised against the disease by infection with live parasites and simultaneous drug treatment, but the immunity induced by one parasite strain is not effective against all other strains. Use of a mixture of 3 parasite strains for vaccination has been found to give broad protection. This vaccine has been used locally with some success, but widespread application has been hindered by difficulties in production and distribution. The antigenic composition of the vaccine is poorly defined and there remain questions as to whether the content of parasite strains is optimal for obtaining robust immunity. More recently, antigens recognised by the protective cellular immune responses have been identified, with the aim of investigating their potential for developing a subunit vaccine. Preliminary evidence indicates that several of these antigens vary between parasite strains. Hence, understanding antigenic variability in T. parva is a key issue both for improving the current live vaccine and for the design of a sub-unit vaccine. The overall aim of the current project is to understand the antigenic basis of strain restricted immunity to T. parva, in order to develop improved vaccines against ECF. The key elements of the proposed research are: - An analysis of T. parva isolates from naturally infected cattle in different regions of Kenya, to determine the nature and extent of antigenic diversity in the parasite population. - An analysis of antigenic diversity in the 3 parasite isolates that make up the current live vaccine. - A detailed study of how variation in the antigens affects the ability of the cellular immune response to recognise different parasite strains. - An analysis of the specificity of cellular immune responses in cattle immunised sequentially and simultaneous with different parasite strains, to understand how these immunisation procedures affect the fine specificity of the immune response. - Analysis of immune Friesian cattle of different MHC genotypes for their ability to recognise currently defined T. parva antigens, in order to identify priorities for further antigen screening. It is anticipated that the results will provide methods for improving quality control of the current live vaccine, identify parasite strains that could be incorporated into an improved second generation live vaccine and indicate which and how many antigens will need to be incorporated into a subunit vaccine. Realisation of the project objectives will ultimately result in improved vaccines for ECF leading to better control of the disease. This will help to secure the assets and increase the incomes of smallholder and pastoral livestock keepers in affected regions. Improved disease control will result in increased production of meat and milk and reduce the levels of poverty in these vulnerable communities.