Synthesis and immunochemical studies on a Candida albicans cluster glycoconjugate vaccine

Abstract

The immunoprotective β-mannan of Candida albicans occurs as part of the cell wall phosphomannan N-linked glycoprotein. This macromolecule is composed of an extended α1,6 linked mannopyranan backbone containing α1,2 mannopyranan branches, to which β1,2 mannopyranan epitopes are attached. The synthesis of β1,2-mannan disaccharides clustered on a glucose core has been achieved as a way to imitate the multipoint display of β-mannans in the native glycoprotein. The clustered epitopes were conjugated to tetanus toxoid and bovine serum albumin. Rabbits immunized with tetanus toxoid cluster glycoconjugate gave good antibody titres for the disaccharide cluster or simple trisaccharide epitope (coupled to BSA). The anti-sera also showed strong cross-reactivity with a Candida albicans β-mannan cell wall extract. These immunochemical results are compared with data obtained with non-cluster disaccharide and trisaccharide glycoconjugate antigens. The same conjugates gave substantially lower antibody levels when used to immunize mice.