A Synthetic β‐Mannan Epitope Enables Immunization and Detection of <i>Candida auris</i>

Abstract

ABSTRACT Candida auris is an emerging multidrug‐resistant fungal pathogen for which neither vaccines nor rapid diagnostics are available. Defined fungal glycan epitopes offer a chemically precise route toward both immunization and detection. Here, we show that a synthetic β‐mannan tetrasaccharide, β‐(1,2)Man‐α‐(1,2)Man‐α‐(1,2)Man‐α‐(1,2)Man, functions as a lead epitope against C. auris . Conjugation of this glycan to the carrier protein CRM 197 afforded a glycoconjugate that elicited epitope‐selective immunoglobulin M (IgM) and immunoglobulin G (IgG) responses and reduced fungal burden in kidneys and spleen in a murine disseminated infection model. Monoclonal IgG1 antibodies raised against the same synthetic glycan displayed structure‐dependent recognition of oligomannosides and Candida cells and enabled passive immunization, resulting in reduced fungal burden in the spleen. One antibody enabled the development of a prototype lateral flow assay for rapid detection of multiple Candida species. The defined synthetic β‐mannan epitope connects glycoconjugate immunization with antibody‐based recognition and establishes a chemically defined platform for antifungal intervention and detection.