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β-Glucan chitosan particle provides cross-protection against multi-drug-resistant Candida auris
Shakti Singh1,2, Ashley Barbarino1, Eman G Youssef1
1Infectious Diseases & Immunology Hub, The Lundquist Institute for Biomedical Innovation at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA.
Abstract:
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.
Insights
A novel vaccine using beta-glucan chitosan particles (GCP) shows promise against multidrug-resistant Candida auris infections. GCP vaccination protected mice, reduced fungal burden, and offers a new strategy against this dangerous pathogen.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Multidrug-resistant Candida auris poses a significant threat, causing life-threatening infections with high mortality rates.
- Limited treatment options exist due to widespread antifungal resistance.
- Candida auris cell walls contain beta-glucan and conserved glycoproteins, presenting potential vaccine targets.
Purpose of the Study:
- To evaluate beta-glucan chitosan particles (GCP) as a vaccine candidate against Candida auris.
- To assess the humoral and cellular immune responses induced by GCP vaccination.
- To determine the protective efficacy of GCP against disseminated C. auris infection in a mouse model.
Main Methods:
- GCP were developed and used to vaccinate mice.
- Humoral (IgG) and cellular (IFN-γ, IL-4, IL-17 producing T cells) immune responses were analyzed.
- Vaccinated mice were challenged with C. auris, and survival, fungal burden, and abscesses were assessed.
Main Results:
- GCP vaccination induced robust IgG antibody and T cell responses recognizing C. auris cell wall proteins.
- Anti-GCP antibodies cross-reacted with C. auris isolates from multiple clades.
- Vaccinated mice showed significantly improved survival (40% vs 0%), reduced fungal burden in organs, and fewer abscesses compared to controls.
Conclusions:
- Beta-glucan chitosan particles (GCP) represent a promising vaccine candidate against multidrug-resistant Candida auris.
- GCP vaccination elicits protective immune responses against disseminated C. auris infection.
- This strategy offers a potential new therapeutic approach for combating C. auris infections.
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