A cell wall protein-based vaccine candidate induce protective immune response against Sporothrix schenckii infection

Area of Science:

• Mycology
• Immunology
• Vaccinology

Background:

• Sporotrichosis, a fungal infection caused by Sporothrix schenckii, is increasing globally.
• Conventional antifungal treatments for sporotrichosis exhibit limited efficacy and toxicity.
• There is a critical need for novel therapeutic strategies against sporotrichosis.

Purpose of the Study:

• To evaluate the immunogenicity and protective potential of aluminum hydroxide (AH)-adsorbed S. schenckii cell wall protein (ssCWP)-based vaccines.
• To assess the immune response elicited by ssCWP vaccines in a mouse model of systemic S. schenckii infection.
• To determine the efficacy of ssCWP vaccines against S. schenckii challenge.

Main Methods:

• Two AH-adsorbed ssCWP vaccine formulations were prepared and administered to mice.
• Protein fractionation using SDS-PAGE identified key antigenic components.
• Humoral and cellular immune responses, including antibody production and cytokine release (IL-12, IFN-γ, IL-4, IL-17), were analyzed.
• Fungal adhesion and phagocytosis assays were performed.
• Passive serum transfer experiments were conducted to assess in vivo protection.

Main Results:

• SDS-PAGE revealed nine protein bands, with a 47kDa enolase identified as a potential adhesin.
• Sera from immunized mice recognized specific ssCWP antigens, including the 47kDa enolase.
• Anti-ssCWP sera enhanced fungal phagocytosis and inhibited fungal adhesion to host cells.
• The AH-adjuvanted vaccine elicited a robust Th1/Th2/Th17 immune response, including elevated IL-12, IFN-γ, IL-4, and IL-17.
• Passive transfer of serum from mice vaccinated with the higher-dose AH-adjuvanted formulation conferred significant protection against S. schenckii challenge.

Conclusions:

• The ssCWP-based vaccine formulations, particularly the AH-adjuvanted version, demonstrate significant immunogenicity and protective efficacy in a murine model.
• The study identifies key antigenic targets within S. schenckii cell wall proteins.
• These findings support the development of ssCWP-based vaccines as a promising strategy for controlling sporotrichosis.