β-Glucan chitosan particle provides cross-protection against multi-drug-resistant Candida auris.

Multidrug-resistant fungi, Candida auris, persist in the healthcare environment and colonize human skin and medical devices, causing life-threatening infections with mortality rates approaching ~60% in immunocompromised patients. Because some isolates are resistant to nearly all available antifungal drugs, alternative therapeutic approaches are urgently needed. C. auris cell wall contains β-glucan and highly conserved fungal glycan structures. Moreover, many cell wall proteins are heavily β-glycosylated, and a monoclonal antibody raised against β-glucan has been shown to recognize C. albicans hyphal-regulated cell wall protein (Hyr1p), which has homologous proteins in C. auris. Based on this conversation, we evaluated β-glucan chitosan particles (GCP) as a vaccine candidate and evaluated the humoral and cellular immune responses. GCP induced robust IgG antibody and IFN-γ, IL-4, and IL17 producing T cells that recognized purified C. auris cell wall proteins. Anti-GCP antibodies recognized the cell walls of C. auris isolates from four phylogenetic clades through binding to cell wall glycoproteins. Mice vaccinated with GCP were protected from disseminated C. auris infection (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. These findings support GCP vaccination as a promising strategy against MDR C. auris.