Chemical Synthesis and Immunological Evaluation of Escherichia coli O29, Shigella dysenteriae Serotype 11, and Proteus vulgaris O12 O-Antigen Oligosaccharides.

Escherichia coli (E. coli), Shigella dysenteriae (S. dysenteriae), and Proteus vulgaris (P. vulgaris) are the leading bacterial causes of death and diseases in many countries. Vaccines are economical and effective tools against bacterial infection. Herein, we present the first total synthesis and immunological evaluation of the E. coli O29, S. dysenteriae serotype 11, and P. vulgaris O12 O-antigen decasaccharides, pentasaccharides, and related oligosaccharide fragments. We found that the hexasaccharide, including two repeating units of the core trisaccharide, was the optimal epitope, which was conjugated with the carrier protein CRM197 to furnish a semisynthetic glycoconjugate vaccine. The glycoconjugate vaccine induced a robust antigen-specific immune response, and the antibody sera could recognize the surface O-antigens of E. coli O29. This glycoconjugate vaccine, including a common trisaccharide fragment, existed in many bacterial O-antigens, which can be further used as a potential broad-spectrum vaccine against E. coli, S. dysenteriae, P. vulgaris, and Cronobacter malonaticus (C. malonaticus).