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

Summary

Researchers used a special microarray technology to identify immune responses in blood samples from people infected with Candida yeast. They found that early infections trigger antibodies against certain sugar structures, while later infections produce different antibodies. Three specific sugar molecules showed promise as markers for diagnostic tests and vaccine development against dangerous yeast infections.

Background

Invasive candidiasis caused by Candida species is a major nosocomial infection with high mortality affecting over 1.5 million people annually. Current diagnostic methods have limitations including low sensitivity, long turnaround times, and frequent false positives. Understanding the immune response to Candida infections through antibody profiling could guide development of improved diagnostic and preventive strategies.

Objective

To identify serum antibodies against Candida-related glycans using glycan microarray technology and discover oligosaccharide epitopes that can serve as biomarkers for diagnosis and vaccine development.

Results

IgM antibodies initially targeted β-glucans, while later IgM and IgG antibodies recognized primarily oligomannoses. The β-(1,2)-mannose monomer distinguished different Candida species. Three oligosaccharides emerged as leads for diagnostics and vaccines: β-(1,2)Man-α-(1,2)Man-α-(1,2)Man-α-(1,2)Man, 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.

Conclusion

Glycan microarray analysis successfully identified species-specific and infection-stage-specific antibody responses to Candida. The identified oligosaccharide epitopes represent promising leads for developing lateral flow diagnostic tests and glycoconjugate or monoclonal antibody vaccines against invasive candidiasis.
  • Published in:Proceedings of the National Academy of Sciences USA,
  • Study Type:Clinical Research Study,
  • Source: PMID: 40996794, DOI: 10.1073/pnas.2505340122
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