Vaccines · 2025
Targeting Azole-Resistant Candida albicans: Tetrapeptide Tuftsin-Modified Liposomal Vaccine Induces Superior Immune Protection.
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Khan Masood A, Khan Arif, Alnuqaydan Abdullah M, Albutti Aqel, Alharbi Basmah F, Owais Mohammad
Аннотация
BACKGROUND/OBJECTIVES: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential of a new liposomal vaccine formulation, Tuft-lip-WCAgs, comprising Tuftsin and C. albicans whole cell antigens, in providing immune protection against systemic candidiasis.
METHODS: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-γ and IL-4) from splenocytes.
RESULTS: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 ± 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 ± 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-γ (634 ± 128 pg/mL) and IL-4 (582 ± 82 pg/mL), indicating a balanced Th1/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 ± 197 CFUs/g).
CONCLUSIONS: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis.
METHODS: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-γ and IL-4) from splenocytes.
RESULTS: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 ± 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 ± 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-γ (634 ± 128 pg/mL) and IL-4 (582 ± 82 pg/mL), indicating a balanced Th1/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 ± 197 CFUs/g).
CONCLUSIONS: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis.