Driving protective immune responses by targetting Mycobacterium bovis and foot-and-mouth disease virus antigens to specific dendritic cell subsets

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Objectives: 1) A series of studies will be performed to demonstrate the efficacy of targeting FMDV and Mycobacterium bovis antigens to mixed populations of dendritic cells(DC) using a range of delivery systems. The initial analysis of antigen uptake will be performed using intracellular FACs analysis, enabling high throughput screening. 2) Determine the phenotypic and functional consequences of targeting specific antigens to isolated DC subsets in vitro. The combination of activator and antigen delivery system that results in the maximum number of cells expressing antigen will be used in these more detailed in vitro studies of DC phenotype and function. For each of the two pathogens under investigation, two combinations of activator/ delivery system for each of the four ALDC subsets will be analysed in detail. 3) The most promising methods to target FMDV and Mycobacterium bovis antigens to specific DC subsets in vitro, will be used in adoptive transfer studies to determine the consequences of DC targeting in vivo. The data generated in objectives 1 and 2 will indicate the nature of the immune response stimulated by each ALDC subset in vitro. The best candidate for each pathogen, identified from objectives 1 and 2 i.e. the combination of viral vector/ALDC subset that stimulates appropriate T and B cell responses in vitro, will be taken forward for assessment in vivo. Appropriately activated DCs expressing antigen will be transfered into naive animals and the subsequent immune response analysed. Furthermore, protection will be assessed using challenge models.

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