Immunoproteomics and reverse vaccinology identify a protective T-cell epitope from Fonsecaea pedrosoi for...

Chromoblastomycosis is a chronic neglected tropical mycosis caused predominantly by the melanized fungus Fonsecaea pedrosoi. Current treatments are prolonged and frequently ineffective, highlighting the need for new therapeutic strategies. Here, we applied an integrated immunoproteomic and reverse vaccinology approach to identify immunogenic antigens from F. pedrosoi and evaluate their vaccine potential. Fungal proteins were separated by two-dimensional electrophoresis and immunoreactive proteins were detected using sera from infected mice. Mass spectrometry identified several antigenic proteins, including enolase and previously uncharacterized hypothetical proteins. Computational epitope prediction revealed a peptide candidate (Hp11696; LGFMSAFKASKLIAI) with high predicted affinity for MHC class II molecules. Functional assays demonstrated that Hp11696 stimulated antigen-specific CD4⁺ T-cell proliferation in splenocytes derived from infected animals. Immunization with Hp11696 significantly reduced fungal burden in a murine model of chromoblastomycosis and induced cytokine responses characterized by increased IFN-γ and IL-10 production. Collectively, these findings demonstrate that immunoproteomics-guided antigen discovery can identify protective peptide epitopes from fungal pathogens. The Hp11696 peptide represents a promising candidate for the development of peptide-based vaccines targeting chromoblastomycosis.