A novel linker methodology for the synthesis of tailored conjugate vaccines composed of complex carbohydrate antigens and specific TH-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 TH-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 GM2 to a TH-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.
Dziadek
Sebastian
S
Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 (Canada).
Jacques
Sandra
S
Bundle
David R
DR
D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D002176:Candida albicans / Q000737:chemistry / Q000276:immunology; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005678:G(M2) Ganglioside / Q000737:chemistry / Q000276:immunology; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000276:immunology; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology; D053583:Interleukin-1beta / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018074:Vaccines, Conjugate
D000941:Antigens; D000939:Epitopes; D006001:Glycoconjugates; D006360:Heat-Shock Proteins; D053583:Interleukin-1beta; D010455:Peptides; D018074:Vaccines, Conjugate; D005678:G(M2) Ganglioside