Synthesis and characterization of glycoconjugated products as potential vaccines against tuberculosis

Carbohydrates have important biological roles as in immune response. Mannose receptor (MR) is important for this function, due to its expression on Antigen Presenting cells (APCs) surfaces. 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 to prepare innovative multivalent glycoconjugates useful as anti-bacterial vaccines (against Tuberculosis) by conjugation of these sugars with antigenic proteins, or peptide epitopes, of Mycobactrium tuberculosis. The project was organized in three phases: 1) The aim of the first part is the chemical synthesis and characterization of analogues of natural polymannan (di- and tri-mannan oligosaccharides with α1,6man and/or α1,2man motifs) that will then be tested as specific ligands for APC receptors. 2) The aim of the second part of the research project regards the synthesis of potential nano-glycoproteins vaccines for Tuberculosis, by using particular self-assembling elastin-like recombinamer (ELR) fused with the antigenic sequence of the protein Ag85C. 3) The third part of the project aims for the investigation of the potential use of fullerene as a carrier for both immunogenic sugars and the antigenic peptides in order to create a potential glyco-peptide-conjugate vaccine for TB.