β-1,2-Mannan-based glycoconjugates as potential antifungal vaccines

Phosphorylated di-, tri- and tetra-saccharides of β-1,2-mannan antigen derived from Candida albicans (C. albicans) cell wall were synthesized and covalently conjugated with keyhole limpet hemocyanin (KLH) and human serum albumin (HSA) via a bifunctional linker under mild conditions. The semi-synthetic β-1,2-mannoside–KLH conjugates were evaluated for the immunization of BALB/c mice. The ELISA results revealed that all three conjugates could elicit high levels of specific IgG antibodies and the acquired antisera could effectively identify the β-1,2-mannan epitope. Furthermore, the immunofluorescence and flow cytometry assays also uncovered that the induced antibodies, especially that obtained from immunization with β-1,2-mannotriose–KLH conjugate (1b), could bind well to fungi cell. Eventually, the structure–immunogenicity relationship analysis of β-mannan showed that the length of oligo-β-mannoses had a big impact on their immunogenicity and β-1,2-mannotriose showed the strongest immunogenicity. The results suggested the great potential of β-1,2-mannotriose–KLH conjugate as an antifungal vaccine candidate. [Display omitted] The synthetic β-1,2-mannan–keyhole limpet hemocyanin (KLH) conjugates immunized with or without Freund's adjuvant provoked high titers of β-1,2-mannan-specific total IgG antibodies and the antibodies elicited by β-1,2-mannotriose–KLH conjugate 1b could recognize natural β-1,2-mannan antigen epitope on the Candida albicans (C. albicans) cell, which suggested great potential of β-1,2-mannotriose–KLH conjugate as an antifungal vaccine candidate.