Executive Summary : | Antimicrobial resistance is a significant threat to human health, with an estimated 10 million deaths annually due to antibiotic resistance by 2050. Current vaccine development requires culture, harvest, and isolation of bacterial cell surface carbohydrate under strict biological settings, which requires biosafety labs. Chemical synthesis of these carbohydrates allows for their purification in sufficient quantities and can be achieved in any synthetic laboratory. Enterococcus faecium is a leading cause of hospital-acquired infections (HAIs) and is resistant to almost all classes of antibiotics listed by WHO. To develop a glycoconjugate vaccine against E. faecium, the research project focuses on the synthesis of L-altruronic acid-containing polysaccharide (Pf2), a repeating structure of a hexasaccharide. The synthesis of Pf2 can be achieved using suitably protected monosaccharide building blocks and stereoselective glycosylations between them. The main challenge is accessing the rare L-altroside building block and stereoselective 1,2-cis glycosylations. After achieving the synthesis of the required hexasaccharide, the project could extend to conjugating glycan antigen with either carrier protein or an effective adjuvant to create an immunogenic vaccine construct that elicits protective IgG antibodies. The synthesis of this antigenic glycan would be the first step towards developing a vaccine against E. faecium infections, and once the proof of concept works in animal models, it would further support the effectiveness of synthetic glycan approaches against other infectious diseases. |