β-Glucan Chitosan Particle Provides Cross-Protection Against Multi-Drug- Resistant Candida auris

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Candida auris is a multidrug-resistant fungal pathogen that can survive outside the host, readily spread, and colonize healthcare environments, medical devices, and human skin. C. auris causes serious, life-threatening infections with mortality rates of ~60% in immunosuppressed patients. Some isolates of C. auris are resistant to virtually all clinically available antifungal drugs. Therefore, alternative therapeutic approaches are urgently needed. C. auris cell wall contains β-glucan, similar to that of non-pathogenic yeasts such as Saccharomyces cerevisiae. Moreover, cellular proteins are also heavily glycosylated with β-1,3and β-1,6 glycan structures. Recently, a monoclonal antibody raised against β-glucan was shown to recognize C. albicans hyphal-regulated cell wall protein (Hyr1p), which has a closely related family of proteins in C auris. We tested β-glucan-chitosan particles (GCP) as a vaccine candidate and evaluated humoral and cellular immune responses. Interestingly, GCP induced robust IgG antibody andTh1/Th2/ Th17 immune responses that cross-reacted with purified C. auris cell wall. Anti-GCPantibodies recognized the cell walls of C. auris isolates from four major clades through binding to cell wall glycoproteins. Mice vaccinated with GCP were protected from disseminatedC. auris infectioncompared to placebo mice (40% vs. 0% survival, p = < 0.0001). GCP-vaccinated mice had significantly lower fungal burden than placebo in target organs (kidney, heart, and brain) and fewer fungal abscesses. The mechanism of protection appeared to require antibodies and T-cell activation. These data represent an important step toward developing an effective vaccine strategy against multidrug-resistant C. auris.

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