Klebsiella pneumoniae (KP) naturally colonizes the mucosal surfaces of healthy people and cause severe infections in immunosuppressed patients resulting in high mortality. The lipopolysaccharide (LPS) O-antigens of KP is the major cause of antibiotic resistant nosocomial infections. They exhibit limited serotype diversity depending on the glycan composition and structure of the O-antigen repeating units. The most prevalent KP O-antigen serotypes differ in the type of monosaccharide galactose (O1 and O2) or mannose (O3, O3a, O3b and O5) as well as the number, linkage and stereochemistry within the O-antigen repeating units. The antibodies generated against LPS O-antigen of KP against human showed distinct patterns of in vivo cross-reactivity, specificity and protection against different clinically relevant KP serotypes.
The first efficient synthetic access to the oligosaccharides of O3 and O5 antigens using solution and automated syntheses has been achieved. The obtained oligosaccharides were conjugated to CRM197 and immunological evaluated towards the development of a KP LPS O-antigen based semi-synthetic glycoconjugate vaccine.
Linear structures of mannan-based O3, O3a, O3b and O5 KP O-antigens; methyl (Me); phosphate (P); mannose (Man); α-anomers (α; blue) and β-anomers (β; red); C1–C2 (green) and C1–C3 (orange) glycosidic linkages; the common part and lipid A (CP)
