Synthesis of bacterial oligosaccharides for vaccine development
Chemical and chemoenzymatic approaches developed by the Boons group have been employed to prepare microbial oligosaccharides to investigate their immunological properties and for the development of vaccines and adjuvants. It includes the chemical synthesis and immunological evaluation of the inner-core oligosaccharide of Klebsiella pneumoniae and Francisella tularensis, exopolysaccharide fragments from Pseudomonas aeruginosa to map epitope requirements of therapeutic monoclonal antibodies, and secondary cell wall polysaccharides from Bacillus anthracis for vaccine and diagnostics development. We have identified unique epitopes in the exopolysaccharide fragments from P. aeruginosa for vaccine development. Methodologies have been introduced for bioconjugation and make it possible to attach saccharides in a controlled manner to carrier proteins.
Chapman RN, Liu L, Boons GJ (2018) 4,6-O-Pyruvyl ketal modified N-acetylmannosamine of the secondary cell wall polysaccharide of Bacillus anthracis is the anchoring residue for its surface layer proteins. J Am Chem Soc 140(49):17079–17085.
Sychantha D, Little DJ, Chapman RN, Boons GJ, Robinson H, Howell PL, Clarke AJ (2018) PatB1 is an O-acetyltransferase that decorates secondary cell wall polysaccharides. Nat Chem Biol 14(1):79-85.
Liu L, Zha J, DiGiandomenico A, McAllister D, Stover CK, Wang Q, Boons GJ (2015) Synthetic enterobacterial common antigen (ECA) for the development of a universal immunotherapy for drug-resistant Enterobacteriaceae. Angew Chem Int Ed 54(37): 10953-10957.
Li H, Mo K., Wang Q, Stover CK, DiGiandomenico A, Boons GJ (2013) Epitope mapping of monoclonal antibodies using synthetic oligosaccharides uncovers novel aspects of immune recognition of the Psl exopolysaccharide of Pseudomonas aeruginosa. Chem Eur J 19(51): 17425-17431.