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Glycan microarray analysis of Candida-related antibodies in human and mice sera guides biomarker discovery and vaccine development

Summary

Researchers developed a test using synthetic sugar molecules found on Candida yeast to detect antibodies in blood from infected patients and mice. They discovered that the immune system produces different antibodies at different stages of infection, starting with antibodies against certain sugars and later focusing on others. The study identified three specific sugar structures that could be used to create simple blood tests to diagnose Candida infections and potentially develop vaccines to prevent these serious fungal infections.

Background

Invasive candidiasis caused by Candida species is a major nosocomial infection affecting over 1.5 million people annually with approximately one million deaths. Current diagnostic methods for candidemia have limitations including low sensitivity, specificity, and long turnaround times. Understanding the immune response to Candida infections through antibody detection is essential for developing better diagnostic and preventive strategies.

Objective

This study aimed to identify Candida-related glycan epitopes using synthetic glycan microarrays to detect serum antibodies (IgG and IgM) in infected humans and mice. The goal was to discover specific oligosaccharide biomarkers that could be used for development of diagnostics and vaccines against invasive candidiasis.

Results

IgM antibodies were initially directed against β-glucans shortly after infection, while later IgM and IgG antibodies predominantly recognized oligomannoses. Species-specific differences were identified, with β-(1,2)-mannose monomer distinguishing C. krusei and phosphodiester-linked mannosides distinguishing other species. Three oligosaccharides emerged as promising vaccine/diagnostic candidates: a tetrasaccharide and two pentasaccharides containing specific mannose and glucose linkages.

Conclusion

Glycan microarray analysis successfully identified infection-specific antibody responses to defined Candida glycan epitopes in both humans and mice. The identified oligosaccharide antigens hold promise for development of monoclonal antibody lateral flow tests, glycoconjugate vaccines, and improved diagnostic strategies for invasive candidiasis.
  • Published in:Proceedings of the National Academy of Sciences USA (PNAS),
  • Study Type:Clinical Study with Animal Model Validation,
  • Source: PMID: 40996794, DOI: 10.1073/pnas.2505340122
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