IMMUNE RESPONSE TO COCCIDIOIDES IMMITIS PROLINE RICH ANTIGEN

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DESCRIPTION (Adapted from application): The investigators propose to analyze recombinant proline-rich antigen (PRA) for differences in immunogenicity along its length. Based on analyses of other T cell-stimulating antigens from several other pathogens including the dimorphic fungi Histoplasma capsulatum and Paracoccidioides brasiliensis, it is anticipated that there exist regions of immunodominance. In some cases, antigenicity can be mapped to specific epitopes. A precise understanding of the location of immunoreactivity could lead to improved vaccine effectiveness by removing inhibitory or toxic portions of the molecule from the vaccine candidate. Furthermore, determining the smallest effective unit of PRA would increase the feasibility for more antigens to be included in a multivalent vaccine strategy. Specific aims for this project will be: 1) characterize protection of the full length PRA with respect to vaccine dose, adjuvant requirements, and range of inbred mouse; 2) compare four recombinant overlapping peptides that span the full length of PRA for differences and interactions in producing protection; 3) map immunoreactivity of a specific quadrant of PRA using synthetic oligopeptides as probes of immunization resulting from vaccination. In parallel to the studies of protection, the investigators will examine the correlation of surrogate markers to observed protection. Immunologic tests will be selected for their practical relevance to future human vaccine trials and will include lymphocyte transformation, cytokine production in response to antigenic stimulation, and footpad swelling as an indicator of delayed-type hypersensitivity. Finally, the investigators plan to extend their evaluation of PRA to its capacity to protect against intranasal infection, which historically has been viewed as a more stringent test of vaccine potency.