Next-generation Candida albicans recombinantAls3p and Hyr1p dual antigen vaccine for invasiveCandida infections

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Candida species, including Candida albicans and Candida auris, represent a growing public health concern due to their increasing prevalence and resistance to antifungal agents. C. albicans is known for causing both superficial and invasive infections, while C. auris is associated with high rates of antifungal resistance. auris is a newly emerged, multidrug-resistantpathogen responsible for severe hospital outbreaks with a high mortality rate of ~ 60% in bloodstreaminfections. Vaccine candidates targetingC. Candida albicans hyphal cell wall proteins Als3p and Hyr1p have shown protective efficacy in mice. NDV-3A, an alum-formulated Als3p-based vaccine, protects againstrecurrent vulvovaginal candidiasis in women. We previously showed that both Als3p and Hyr1p have orthologs in C. auris, and that the NDV-3A vaccine, alongside an anti-Hyr1p monoclonal antibody, protects mice from lethal C. auris candidemia. Here, we optimized Als3p and Hyr1p dual antigen vaccineformulations with the clinical-stage adjuvant CAF01, demonstrating robust immunity and CD4 T cell-dependent protection against lethalC. albicans andC. auris. The vaccine formulations also showedenhanced protective efficacy when combined with antifungal drugs. This study highlights the potential of the CAF01-formulated Als3p/Hyr1p dual-antigen vaccine to elicit durable protective immunity against systemic and mucosal C. albicans infections and to confer cross-protection against systemic multidrug-resistant C.auris infections.

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