Immunogenicity and efficacy of CNA25 as a potential whole-cell vaccine against systemic candidiasis

Area of Science:

• Mycology
• Immunology
• Vaccinology

Background:

• Disseminated fungal infections cause significant mortality globally.
• Increasing immunocompromised populations and antifungal resistance exacerbate this threat.
• There is a critical need for effective antifungal vaccines.

Purpose of the Study:

• To investigate the immunogenicity and vaccine efficacy of a DNA polymerase mutant strain of Candida albicans (CNA25).
• To evaluate CNA25's protective potential against systemic candidiasis in a murine model.

Main Methods:

• Utilized a pol32ΔΔ mutant strain of Candida albicans (CNA25) with impaired growth and virulence.
• Assessed vaccine efficacy in mice immunized with live CNA25 against various Candida species infections.
• Analyzed immune responses, including receptor expression (TLR2, Dectin-1) and immune cell activation (neutrophils, macrophages, NK, B, T cells).
• Investigated the role of specific immune mediators (Dectin-1, IL-17, IFNγ, TNFα) via molecular blockade.

Main Results:

• CNA25 immunization conferred full protection against Candida albicans and Candida parapsilosis, and partial protection against Candida tropicalis and Candida glabrata.
• CNA25 induced sustained expression of TLR2 and Dectin-1, enhancing immune recognition and clearance.
• Immune activation involved neutrophils, macrophages, NK cells, B cells, and CD4+/CD8+ T cells.
• Blocking Dectin-1, IL-17, IFNγ, or TNFα abrogated the vaccine-induced resistance.

Conclusions:

• CNA25 demonstrates significant immunogenicity and vaccine efficacy against systemic candidiasis.
• The vaccine candidate activates innate, adaptive, and trained immunity.
• CNA25 represents a promising live whole-cell vaccine strategy for preventing disseminated fungal infections.