Tuberculosis (TB) has plagued mankind for millennia. While several drugs and vaccine strategies have been developed to counter the TB, it remains a major infectious cause of morbidity and mortality worldwide. 1. Though the elucidation of the M. tuberculosis genome may yield novel drug targets, an efficacious vaccine strategy is key to controlling this infectious disease. 2. Recent research describing the immunopathology of TB infection and the innate immune system reveals a novel vaccination approach utilizing non-peptide based antigens. 3. Glycolipid-based molecules demonstrate the ability to generate a strong, cell mediated immune response, which is thought to be critical against M. tuberculosis. A predominant M. tuberculosis glycolipid molecule, lipoarabinomannan (LAM), also can elicit a strong immune response. The goal of this SBIR proposal will be to generate synthetic LAM-derived, glycolipid-based, molecules that can serve as potential TB vaccine candidates.
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