Current methods for assessing vaccine candidates for preventing coccidioidomycosis yield different results with different test conditions, limiting their usefulness. To improve this situation, this project will first develop histopathologic profiles of host response to infection in the lungs of genetically resistant mice (DBA), both naive and FKS vaccinated, and compare this profile to the response in FKS vaccinated and unvaccinated genetically susceptible mice (C57BL/6). Immunohistochemical stains for cell-type specific membrane markers and cytokines will be applied to lung tissue over a time course following infection. The results will guide selected analyses of bronchoalveolar lavage fluid (BALF) by 2D PAGE and mass spectrometry to identify additional proteins associated with resistance and guide additional analyses of tissue by in situ hybridization with cytokine probes. These pulmonary responses for susceptible and resistant mice will be compared to those produced by recombinant antigens in various vaccination protocols. These analyses should identify vaccine formulations and protocols that result in histologic patterns closest to those found with resistance, either genetic or FKS-produced. In addition, this project will draw comparisons between the pulmonary histopathology of experimental murine infections and histologic material from human surgical specimens obtained during local clinical practice.