Paracoccidioides HSP90 Can Be Found in the Cell Surface and Is a Target for Antibodies with Therapeutic Potential

Area of Science:

• Mycology
• Immunology
• Infectious Diseases

Background:

• Paracoccidioidomycosis (PCM) is a prevalent systemic mycosis in Latin America, primarily affecting rural male workers.
• Current PCM therapies are lengthy (up to two years) and involve toxic drugs, necessitating safer and more effective treatments.
• Heat Shock Protein 90 (HSP90) is a crucial fungal virulence factor, making it a potential therapeutic target.

Purpose of the Study:

• To develop and evaluate a monoclonal antibody (mAb) targeting fungal HSP90 for potential PCM immunotherapy.
• To assess the antibody's ability to modulate host antifungal immunity and target fungal cells.

Main Methods:

• Recombinant HSP90 proteins from *Paracoccidioides lutzii* and *P. brasiliensis* were used to immunize mice.
• Polyclonal antibodies and a hybridoma monoclonal antibody (mAb) were generated.
• Immunofluorescence assays were performed to detect antibody binding to fungal cell surfaces.
• Opsonization assays were conducted using macrophage-like cells (J774.16) to assess phagocytosis enhancement.

Main Results:

• The recombinant HSP90 proteins were immunogenic, eliciting both polyclonal and monoclonal antibody responses.
• The generated mAb demonstrated specific binding to the surface of *P. lutzii* and *P. brasiliensis* yeast cells.
• The mAb effectively opsonized fungal cells, promoting their uptake by macrophages.

Conclusions:

• A novel mAb targeting fungal HSP90 has been successfully generated.
• This mAb shows potential as a basis for new immunotherapy strategies against Paracoccidioidomycosis.
• The findings suggest a promising approach to combatting this significant fungal infection.