A Synthetic β-Mannan Epitope Enables Immunization and Detection of Candida auris.

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 CRM197 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.