A synthetic peptide vaccine induces protective immune responses against Candida albicans infection in immunocompromised mice

Invasive fungal infections, such as those caused by Candida species, predominantly affects hospitalized and immunocompromised patients. Current mortality rates are expected to rise as drug-resistant fungal species increase and the pool of immunocompromised individuals grows. Today, antifungal treatments show limited effectiveness, underscoring the need for new safe and effective antifungal vaccines. This study investigates the efficacy of a protective immunization strategy with DC stimulated by a synthetic peptide, 3P-KLH, containing epitopes from three Candida albicans proteins (Als3, Hwp1 and Met6) against a model of invasive candidiasis raised in immunosuppressed mice. Immunization effectively stimulated both humoral and cellular immune responses, as indicated by high antibody titers to the synthetic fungal peptide, increased cytokine levels, reduced fungal burden in kidneys and improved survival outcomes following infection.

Although the variability in fungal burden in the control group limited the statistical significance for fungal clearance data, immunized mice showed a 64-fold lower fungal burden in renal tissues compared to controls. Cytokine analysis revealed elevated levels of IL-2, IL-17, and IFN-γ, suggesting a strong activation of Th1 and Th17 responses, both essential for antifungal immunity.

Survival data further supported the protective effect of the immunogenic agent: 62.5 % immunized mice survived the 21-day post-infection period compared to 100 % mortality in controls. The progressively lower fungal burden over time in surviving mice suggests a sustained immune response that continues to suppress fungal replication. These results suggest that the immunization with the synthetic peptide stimulates a strong immune response, involving both antibody production and cell-mediated immunity, making it a promising candidate for therapeutic strategies against invasive candidiasis. Future work should focus on optimizing this immunization approach, assessing long-term immunity, and evaluating its potential in other fungal infection models.