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

Autor: Kowarik M; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland. michael.kowarik@lmtbio.com.; LimmaTech Biologics AG, Grabenstrasse 3, 8952, Schlieren, Switzerland. michael.kowarik@lmtbio.com., Wetter M; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093, Zürich, Switzerland., Haeuptle MA; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; Molecular Partners AG, Wagistrasse 14, 8952, Schlieren, Switzerland., Braun M; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; LimmaTech Biologics AG, Grabenstrasse 3, 8952, Schlieren, Switzerland., Steffen M; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; LimmaTech Biologics AG, Grabenstrasse 3, 8952, Schlieren, Switzerland., Kemmler S; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; Numab Therapeutics AG, Einsiedlerstrasse 34, 8820, Wädenswil, Switzerland., Ravenscroft N; Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa., De Benedetto G; Dip. di Scienze della Vita, University di Trieste, 34127, Trieste, Italy.; National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK., Zuppiger M; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; LimmaTech Biologics AG, Grabenstrasse 3, 8952, Schlieren, Switzerland., Sirena D; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; LimmaTech Biologics AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; GlycoEra AG, Grabenstrasse 3, 8952, Schlieren, Switzerland., Cescutti P; Dip. di Scienze della Vita, University di Trieste, 34127, Trieste, Italy., Wacker M; GlycoVaxyn AG, Grabenstrasse 3, 8952, Schlieren, Switzerland.; Wacker Biotech Consulting AG, Heuelstrasse 22, 8800, Thalwil, Switzerland.
Jazyk: angličtina
Zdroj: Glycoconjugate journal [Glycoconj J] 2021 Aug; Vol. 38 (4), pp. 421-435. Date of Electronic Publication: 2021 Mar 17.
DOI: 10.1007/s10719-021-09985-9
Abstrakt: Extraintestinal pathogenic Escherichia coli (ExPEC) cause a wide range of clinical diseases such as bacteremia and urinary tract infections. The increase of multidrug resistant ExPEC strains is becoming a major concern for the treatment of these infections and E. coli has been identified as a critical priority pathogen by the WHO. Therefore, the development of vaccines has become increasingly important, with the surface lipopolysaccharide constituting a promising vaccine target. This study presents genetic and structural analysis of clinical urine isolates from Switzerland belonging to the serotype O25. Approximately 75% of these isolates were shown to correspond to the substructure O25B only recently described in an emerging clone of E. coli sequence type 131. To address the high occurrence of O25B in clinical isolates, an O25B glycoconjugate vaccine was prepared using an E. coli glycosylation system. The O antigen cluster was integrated into the genome of E. coli W3110, thereby generating an E. coli strain able to synthesize the O25B polysaccharide on a carrier lipid. The polysaccharide was enzymatically conjugated to specific asparagine side chains of the carrier protein exotoxin A (EPA) of Pseudomonas aeruginosa by the PglB oligosaccharyltransferase from Campylobacter jejuni. Detailed characterization of the O25B-EPA conjugate by use of physicochemical methods including NMR and GC-MS confirmed the O25B polysaccharide structure in the conjugate, opening up the possibility to develop a multivalent E. coli conjugate vaccine containing O25B-EPA.
Databáze: MEDLINE
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