Disclosed are protein and peptide antigen and DNA compositions effective in generating immune responses against the pathogenic fungi Coccidioides spp., the causative agents of coccidioidomycosis and Valley Fever. The invention thus provides protein and peptide antigens, DNA constructs, combinations and related biological compositions, and prophylactic and therapeutic methods of using such components and combinations to generate effective and protective immune responses against Coccidioides spp., including C. immitis.