A chemically synthesized fungal sugar elicited protective immune responses against Candida auris in mice and provided the basis for a prototype antibody diagnostic, according to a study published August 11 in Angewandte Chemie International Edition. The findings establish a defined β-mannan epitope as a potential platform for active vaccination, passive antibody therapy and detection of the multidrug-resistant fungal pathogen, although all therapeutic findings remain preclinical.
The work was conducted by researchers including Peter H. Seeberger at Germany's Max Planck Institute of Colloids and Interfaces and Neil A. R. Gow and Alistair J. P. Brown at the University of Exeter. C. auris has emerged as a major cause of difficult-to-treat invasive infections and healthcare-associated outbreaks, with resistance to multiple antifungal drugs reported. No fungal vaccine is approved for human use, creating interest in immunization strategies that could prevent or reduce invasive infection.
The researchers focused on M13, a synthetic β-(1,2)-mannan tetrasaccharide representing an immunologically relevant carbohydrate structure found on the fungal cell surface. Natural fungal polysaccharides are structurally heterogeneous, complicating the development of precisely defined vaccine antigens. The team instead synthesized M13 and conjugated it to CRM197, a non-toxic diphtheria toxin-derived carrier protein used in licensed conjugate vaccines, producing a glycoconjugate containing an average of approximately 14 glycan units per carrier protein.
Immunization with M13-CRM197 induced epitope-specific IgM followed by IgG responses in mice. In a disseminated infection experiment, vaccinated animals challenged with a clade I C. auris isolate had significantly lower fungal burdens in the kidneys and spleen than controls. Higher IgG levels correlated with lower fungal burden, providing evidence that immune responses directed against the synthetic glycan can contribute to control of infection. The study did not establish protection against all major C. auris clades, although antibodies generated by immunization recognized isolates representing clades I–IV.
The researchers also generated three IgG1 monoclonal antibodies, designated 7HF, 7KH and 7CG, against the synthetic epitope. Their functional effects differed despite recognition of related β-mannan structures. In passive immunization experiments, 7HF significantly reduced fungal burden in the spleen but not the kidney, while 7KH did not confer protection and was associated with increased kidney fungal burden. The findings suggest that recognition of the glycan epitope alone is insufficient to predict whether an antibody will provide protection, with Fc-mediated activity, tissue distribution and other properties potentially influencing efficacy.