SYNTHESIS AND CHARACTERIZATION OF GLYCOCONJUGATED PRODUCTS AS POTENTIAL VACCINES AGAINST TUBERCULOSIS

Carbohydrates are an important class of biomolecules. Usually they are covalent linked with other macromolecules as lipid or proteins. They have important biological roles in receptor functions, cell adhesion, cell-cell signalling, in inflammation and above all in immune response. Mannose receptor (MR) is important for this last function: due to its expression on Antigen Presenting cells (APC) surfaces, MR are involved in immune process. The interaction between oligosaccharides exposed on cell surface of pathogens and mannose receptor induces the internalization, processing and exposition of the antigen on the APC cells surface (the first event in the immune response). The discovery of the role of MR has stimulated the research towards the development of mannosylated antigens in order to increase immune response. Natural polymannan or its analogues, being well-recognized by mannose receptor of APC, could be used in order to improve the antigenic activity of peptide or proteins by mannosylation. The aim of the project is preparing innovative multivalent glycoconjugates useful as anti-bacterial vaccines (against Tuberculosis) by conjugation of these sugars with antigenic proteins, or peptide epitopes, of Mycobactrium tuberculosis (MTB). In particular a self-assembling elastin-like recombinamer (ELR) fused with the antigenic sequence of the protein Ag85B was considered as scaffold for the development of glyco-conjugated nano vaccines. The use of fullerene as scaffold for glycosylation has also been considered.