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A Novel Linker Methodology for the Synthesis of Tailored Conjugate Vaccines Composed of Complex Carbohydrate Antigens and Specific T H ‐Cell Peptide Epitopes
Author(s) -
Dziadek Sebastian,
Jacques Sandra,
Bundle David R.
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800065
Subject(s) - epitope , glycopeptide , biotinylation , peptide , antigen , linker , candida albicans , biochemistry , glycoprotein , chemistry , conjugate vaccine , biology , microbiology and biotechnology , immunogenicity , immunology , computer science , operating system , antibiotics
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)‐β‐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‐1β (IL‐1β), and for the conjugation of complex carbohydrates to carrier proteins such as bovine serum albumin.