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<p>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 <i>Candida albicans</i>. While the deletion of <i>POL32</i> in a hyper-virulent <i>rad30</i>ΔΔ strain attenuated the virulence, the deletion of <i>RAD30</i> in an avirulent <i>pol32</i>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.</p>

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Characterization of dual DNA polymerase knockout strains of Candida albicans with live whole-cell vaccine competence

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Abinash Dutta,
  • Satya Ranjan Sahu,
  • Bhabasha Gyanadeep Utkalaja,
  • Sushree Subhashree Parida,
  • Shraddheya Kumar Patel,
  • Premlata Kumari,
  • Narottam Acharya

摘要

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 rad30ΔΔ strain attenuated the virulence, the deletion of RAD30 in an avirulent pol32ΔΔ 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.