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Characterization of dual DNA polymerase knockout strains of Candida albicans with live whole-cell vaccine competence
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Characterization of dual DNA polymerase knockout strains of Candida albicans with live whole-cell vaccine competence
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Characterization of dual DNA polymerase knockout strains of Candida albicans with live whole-cell vaccine competence
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Journal Article
Characterization of dual DNA polymerase knockout strains of Candida albicans with live whole-cell vaccine competence
2025
Overview
Systemic candidiasis inflicts ~1.2 million deaths annually worldwide. Despite its severity, an approved antifungal vaccine remains an unmet human need. In a quest to design a live-whole cell vaccine, we characterized and demonstrated the vaccine potential of two dual DNA polymerase-defective strains of
Candida albicans
. While the deletion of
POL32
in a hyper-virulent
rad30
ΔΔ strain attenuated the virulence, the deletion of
RAD30
in an avirulent
pol32
ΔΔ did not revert to a hypervirulence phenotype. Both the dual polymerase-defective strains replicate transiently in the host and trigger immune responses to prevent reinfections in mice by employing a concerted involvement of innate, adaptive, and trained immunity. The cellular and molecular depletion in immunized mice suggested the role of B- and T-cells, neutrophils, and macrophages in antifungal immunity. Altogether, our results confirmed that Pol32 is a true virulence factor and intravenous vaccination with these attenuated strains could prevent systemic candidiasis in the preclinical models without evident safety concerns; thus, these candidate strains have enormous translational potential to fully develop as antifungal vaccines.
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