Professor Geert-Jan Boons, PhD, Complex Carbohydrate Research Center, University of Georgia (Host: Prof. Weiping Tang)

Fully Synthetic Carbohydrate-Based Vaccines and Immune Modulators

We employ well-defined complex synthetic oligosaccharides and glycoconjugates to probe biological processes and use the resulting information to devise novel therapeutic strategies for various diseases.  We have designed, chemically synthesized and immunologically evaluated a number of fully synthetic vaccine candidates to establish strategies to overcome the poor immunogenicity of tumor-associated carbohydrates and glycopeptides.  It has been found that a glycosylated MUC1 derived glycopeptide covalently linked to a Toll-like receptor (TLR) agonist can elicit potent humoral and cellular immune responses and is efficacious in reversing tolerance and generating a therapeutic response.  The examination of a number of control compounds demonstrate that the therapeutic effect of the three-component vaccine is due to nonspecific antitumor responses elicited by the adjuvant, and specific humoral and cellular immune responses elicited by the MUC1 derived glycopeptide.  It has been found that glycosylation of the MUC1 peptide is critical for inducing optimal responses and furthermore, it is essential that the helper T- and B-epitope are covalently attached to the TLR ligand.  To identify new tumor associated carbohydrate antigens, 4-dibenzocyclooctynol derivatives have been developed as novel click reagents for the isolation and visualization of oligosaccharides of living cells that are metabolically labeled with azido containing monosaccharides.  The new reagent has been used for the development of a quantitative glycoproteomics approach.

Room 2006 Rennebohm Hall