SiSHo

Bioconjugates refer to as biomolecules – proteins, nucleic acids, or sugars – covalently linked together or to drugs, fluorescent probes, polyethylene glycol polymers… Bioconjugates are increasingly important in the fields of materials, biotechnology, nanotechnology and medicine. Among them, glycoconjugate vaccines formed from polysaccharide antigens linked to a so-called carrier protein offer protection against many bacterial infections. However, the process for preparing glycoconjugate vaccines remains largely empirical and leads to mixtures of conjugates that are not reproducible from batch to batch, which are difficult to characterize and whose immunogenicity is not completely controlled. In addition, these vaccines only allow the recruitment of a restricted population of immune cells. This project combines the power of organic synthesis to prepare synthetic oligosaccharide antigens mimicking commonly used polysaccharides and adjuvant molecules, cell engineering to obtain carrier proteins, decorated in a targeted manner with bioorthogonal functions by the combination of mutagenesis techniques or incorporation of unnatural amino acids and the implementation of efficient bioconjugation reactions to allow the assembly of the different partners in order to obtain for the first time fully homogeneous self-adjuvanted glycoconjugate vaccines. The immunogenicity of these molecular glycoconjugates will be evaluated in vitro and in vivo in mice in a model of pneumococcal infection.