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Profiling Anti-Neu5Gc IgG in Human Sera with a Sialoglycan Microarray Assay
Published on: July 13, 2017
Glycan microarray analysis of Candida-related antibodies in human and mice sera guides biomarker discovery and
Emelie E Reuber1,2, Emer Hickey3, Arnab Pradhan3
1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin 14195, Germany.
Abstract:
Invasive, high-mortality yeast infections caused by pathogenic Candida species are the most common fungal nosocomial bloodstream infections. The World Health Organization (WHO) has called for improved prevention and diagnostic strategies for fungal pathogens. Here, we demonstrate that Candida-related antibodies can be detected using glycan microarrays containing synthetic glycans to guide the discovery of oligosaccharide epitopes for diagnostics and vaccine design. Pure, synthetic mannans and β-glucans, resembling carbohydrates found on the surface of Candida spp., were employed to screen and compare sera from infected humans and mice with noninfected individuals. IgM antibodies directed toward β-glucans were observed shortly after infection, and after a longer time of infection, IgM and IgG antibodies that preferentially recognize mannans. Phosphodiester-linked mannosides and the β-(1,2)-mannose monomer help to distinguish different Candida spp. The tetrasaccharide antigen β-(1,2)Man-α-(1,2)Man-α-(1,2)Man-α-(1,2)Man, and the pentasaccharide antigens α-(1,2)Man-α-(1,3)Man-α-(1,2)Man-α-(1,2)Man-α-(1,2)Man and β-(1,3)Glc-β-(1,3)Glc-β-(1,3)Glc-[β-(1,6)Glc]-β-(1,3)Glc were identified as potential epitopes for detection, e.g., through monoclonal antibody lateral flow tests, and the development of glycoconjugate or monoclonal antibody vaccines against Candida.
Insights
Researchers identified specific carbohydrate structures on Candida yeast that trigger antibody responses in infected individuals. These findings can aid in developing new diagnostic tools and vaccines for invasive fungal infections.
Area of Science:
- Immunology
- Mycology
- Carbohydrate Chemistry
Background:
- Invasive Candida infections are common, deadly hospital-acquired fungal bloodstream infections.
- The World Health Organization (WHO) emphasizes the need for better fungal pathogen diagnostics and prevention.
- Current diagnostic and therapeutic strategies for Candida infections require improvement.
Purpose of the Study:
- To identify specific Candida-associated carbohydrate epitopes recognized by human and mouse antibodies.
- To explore the potential of these epitopes for developing novel diagnostic assays and vaccines.
- To differentiate Candida species using distinct glycan structures.
Main Methods:
- Utilized glycan microarrays with synthetic mannans and β-glucans.
- Screened sera from infected humans and mice against non-infected controls.
- Analyzed antibody (IgM and IgG) recognition patterns.
Main Results:
- Detected IgM antibodies against β-glucans early in infection.
- Observed IgM and IgG antibodies recognizing mannans later in infection.
- Identified specific oligosaccharide antigens (tetrasaccharide and pentasaccharide) as potential diagnostic and vaccine targets.
Conclusions:
- Candida-specific antibodies can be detected using synthetic glycans on microarrays.
- Identified oligosaccharide epitopes offer potential for diagnostic tests and vaccine development.
- Distinct glycan structures, like phosphodiester-linked mannosides and β-(1,2)-mannose, can help differentiate Candida species.
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