Glycan microarray analysis of <i>Candida</i> -related antibodies in human and mice sera guides biomarker discovery and vaccine development
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>
Authors
- Ian Leaves (ORCID: https://orcid.org/0000-0002-5612-9087)
- Neil A. R. Gow (ORCID: https://orcid.org/0000-0002-2776-5850)
- Peter H. Seeberger (ORCID: https://orcid.org/0000-0003-3394-8466)
- José Danglad‐Flores (ORCID: https://orcid.org/0000-0002-5671-6089)
- Alistair J. P. Brown (ORCID: https://orcid.org/0000-0003-1406-4251)
- Mihai Gheorghe Netea (ORCID: https://orcid.org/0000-0003-2421-6052)
- Leif Erik Sander (ORCID: https://orcid.org/0000-0002-0476-9947)
- Mark H. T. Stappers (ORCID: https://orcid.org/0000-0003-4154-7160)
- Emelie E. Reuber
- Tilman Lingscheid (ORCID: https://orcid.org/0000-0001-5377-3152)
- Arnab Pradhan (ORCID: https://orcid.org/0000-0003-4328-3912)
- Eric T. Sletten (ORCID: https://orcid.org/0000-0003-2177-2969)
- Rosanne Sprute (ORCID: https://orcid.org/0000-0003-2457-6437)
- Emer Hickey (ORCID: https://orcid.org/0000-0002-8971-0310)
- Pinkus Tober‐Lau (ORCID: https://orcid.org/0000-0002-9148-3663)
- Oliver A. Cornely (ORCID: https://orcid.org/0000-0001-9599-3137)
- Florian Kurth (ORCID: https://orcid.org/0000-0002-3807-473X)
- Mariolina Bruno (ORCID: https://orcid.org/0000-0002-5353-7691)
- R. K. Singh (ORCID: https://orcid.org/0000-0002-8602-8498)
- Sabrina Omoregbee‐Leichnitz
Institutions
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- University of Exeter (GB)
- University Medical Center (US)
- Radboud University Medical Center (NL)
- Humboldt-Universität zu Berlin (DE)
- Düsseldorf University Hospital (DE)
- Max Planck Institute of Colloids and Interfaces (DE)
- Integrated Oncology (United States) (US)
- Centre de Recherche Médicales de Lambaréné (GA)
- German Center for Infection Research (DE)
- German Center for Lung Research (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- University Hospital Cologne (DE)
- Life & Brain (Germany) (DE)
- Heinrich Heine University Düsseldorf (DE)
- Freie Universität Berlin (DE)
- Medical Research Council (GB)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1073/pnas.2505340122
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsches Zentrum für Infektionsforschung
- Wellcome Trust
- National Institute for Health and Care Research
- Department of Health and Social Care
- Radboud Universiteit
- Radboud Universitair Medisch Centrum
- Humboldt-Universität zu Berlin
- Universität zu Köln
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Deutsches Zentrum für Lungenforschung
- Universitätsklinikum Köln
- Berlin Institute of Health
- Medical Research Council Centre for Medical Mycology
- Medical Research Council