Glycan microarray analysis of <i>Candida</i>-related antibodies in human and mice sera guides biomarker discovery and vaccine development.

Abstract

Invasive, high-mortality yeast infections caused by pathogenic <i>Candida</i> 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 <i>Candida</i>-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 <i>β</i>-glucans, resembling carbohydrates found on the surface of <i>Candida</i> spp., were employed to screen and compare sera from infected humans and mice with noninfected individuals. IgM antibodies directed toward <i>β</i>-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 <i>β</i>-(1,2)-mannose monomer help to distinguish different <i>Candida</i> spp. The tetrasaccharide antigen <i>β</i>-(1,2)Man-<i>α</i>-(1,2)Man-<i>α</i>-(1,2)Man-<i>α</i>-(1,2)Man, and the pentasaccharide antigens <i>α</i>-(1,2)Man-<i>α</i>-(1,3)Man-<i>α</i>-(1,2)Man-<i>α</i>-(1,2)Man-<i>α</i>-(1,2)Man and <i>β</i>-(1,3)Glc-<i>β</i>-(1,3)Glc-<i>β</i>-(1,3)Glc-[<i>β</i>-(1,6)Glc]-<i>β</i>-(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 <i>Candida.</i>