SYNTHESIS AND CHARACTERIZATION OF GLYCOCONJUGATE VACCINE CANDIDATES AGAINST TUBERCULOSIS

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading cause of death globally, necessitating new vaccination strategies. This thesis reports the synthesis and characterization of glycoconjugate vaccine candidates targeting the mannose receptor (MR) on antigen-presenting cells (APCs). Mannosylation of antigens was hypothesized to enhance their immunogenicity by improving interaction with MR, thereby promoting uptake and antigen presentation. A library of mannose-based oligosaccharides characterized by α(1→2) and α(1→6) linkages was synthesized, functionalized with diverse reactive groups at their anomeric position, and used to glycosylate TB antigens and nanosystems (including antigenic elastin-like recombinamers and fullerene). Mannosylated derivatives were characterized for MR-binding affinity via grating-coupled interferometry and evaluated for immunogenicity in biological assays. Results demonstrated that glycosylation improved antigen interaction with MR, with significant implications for vaccine efficacy. The findings advance our understanding of C-type lectin receptors-targeted (CLR-targeted) strategies and offer insights for developing effective TB vaccines.