Hp11696 peptide vaccine significantly reduces fungal burden in murine chromoblastomycosis model

Chromoblastomycosis is a debilitating neglected tropical mycosis caused predominantly by the melanized fungus Fonsecaea pedrosoi. Current treatments are often prolonged and frequently ineffective, leading to high recurrence rates and significant morbidity. This highlights a critical unmet need for novel therapeutic and preventive strategies. Identifying specific immunogenic antigens that can elicit a protective immune response is crucial for developing effective peptide-based vaccines against this persistent fungal infection, moving beyond broad-spectrum antifungals.

Researchers employed an integrated immunoproteomic and reverse vaccinology approach to identify potential vaccine candidates. Fungal proteins from F. pedrosoi were separated using two-dimensional electrophoresis, and immunoreactive proteins were identified via mass spectrometry using sera from infected mice. Computational epitope prediction was then used to identify a peptide candidate, Hp11696 (LGFMSAFKASKLIAI), with high predicted affinity for MHC class II molecules. Functional assays assessed CD4+ T-cell proliferation in splenocytes from infected animals. Finally, a murine model of chromoblastomycosis was immunized with Hp11696 to evaluate its vaccine potential, with fungal burden and cytokine responses as primary endpoints.

Immunoproteomic analysis identified several antigenic proteins, including enolase and previously uncharacterized hypothetical proteins. Computational prediction successfully identified the Hp11696 peptide as a strong candidate. Functional assays confirmed that Hp11696 stimulated antigen-specific CD4+ T-cell proliferation in splenocytes derived from infected animals, indicating a robust cellular immune response. In the murine model of chromoblastomycosis, immunization with Hp11696 significantly reduced fungal burden. This protective effect was accompanied by a distinct cytokine profile: > Immunization with Hp11696 induced increased IFN-γ and IL-10 production, suggesting a balanced Th1 and regulatory T-cell response crucial for fungal clearance and immune modulation. These findings collectively demonstrate the efficacy of this immunoproteomics-guided approach.