The development and characterization of an E. coli O25B bioconjugate vaccine

• DOI: 10.1007/s10719-021-09985-9
• Publication Date: 2021-03-17T12:03:05Z
• Authors: Michael Kowarik; Michael Wetter; Micha A. Haeuptle; Martin Braun; Michael Steffen; Stefan Kemmler; Neil Ravenscroft; Gianluigi De Bene...; Matthias Zuppiger; Dominique Sirena; Paola Cescutti; Michael Wacker
• Keywords: Conjugate

Extraintestinal pathogenic Escherichia coli (ExPEC) cause a wide range of clinical diseases such as bacteremia and urinary tract infections. The increase multidrug resistant ExPEC strains is becoming major concern for the treatment these infections E. has been identified critical priority pathogen by WHO. Therefore, development vaccines become increasingly important, with surface lipopolysaccharide constituting promising vaccine target. This study presents genetic structural analysis urine isolates from Switzerland belonging to serotype O25. Approximately 75% were shown correspond substructure O25B only recently described in an emerging clone sequence type 131. To address high occurrence isolates, glycoconjugate was prepared using glycosylation system. O antigen cluster integrated into genome W3110, thereby generating strain able synthesize polysaccharide on carrier lipid. enzymatically conjugated specific asparagine side chains protein exotoxin A (EPA) Pseudomonas aeruginosa PglB oligosaccharyltransferase Campylobacter jejuni. Detailed characterization O25B-EPA conjugate use physicochemical methods including NMR GC-MS confirmed structure conjugate, opening up possibility develop multivalent containing O25B-EPA.