A novel linker methodology for the synthesis of tailored conjugate vaccines composed of complex carbohydrate antigens and specific T-H-cell peptide epitopes

Pathogenic organisms or oncogenically transformed cells often express complex carbohydrate structures at their cell surface, which are viable targets for active immunotherapy. We describe here a novel, immunologically neutral, linker methodology for the efficient preparation of highly defined vaccine conjugates that combine complex saccharide antigens with specific T-H-cell peptide epitopes. This novel heterobifunctional approach was employed for the conjugation of a (1 -> 2)-beta-mannan trisaccharide from the pathogenic fungus Candida albicans as well as the carbohydrate portion of tumor-associated ganglioside GM(2) to a T-H-cell peptide epitope derived from the murine 60 kDa self heat-shock protein (hsp60). Moreover, the linkage chemistry has proven well suited for the synthesis of more complex target structures such as a biotinylated glycopeptide, a three component vaccine containing an immunostimulatory peptide epitope from interleukin-1 beta (IL-1 beta), and for the conjugation of complex carbohydrates to carrier proteins such as bovine serum albumin.