Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: invasive nontyphoidal Salmonella disease (iNTS) [ICD11:
1A09 
, ICD11:
XN0QE ];
infection due to Salmonella enterica [ICD11:
XN5VC ]
Publication DOI: 10.1002/anie.201506112Journal NLM ID: 0370543Publisher: Weinheim: Wiley-VCH
Correspondence: qiying.hu
novartis.com; francesca.x.micoli
gsk.com
Institutions: Sclavo Behring Vaccines Institute For Global Health S.r.l., A GSK Company, Via Fiorentina 1, 53100 Siena (Italy), Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, MA 02139 (USA), GSK, Via Fiorentina 1, 53100 Siena (Italy), Jenner Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ (UK)
A series of glycoconjugates with defined connectivity were synthesized to investigate the impact of coupling Salmonella typhimurium O-antigen to different amino acids of CRM197 protein carrier. In particular, two novel methods for site-selective glycan conjugation were developed to obtain conjugates with single attachment site on the protein, based on chemical modification of a disulfide bond and pH-controlled transglutaminase-catalyzed modification of lysine, respectively. Importantly, conjugation at the C186-201 bond resulted in significantly higher anti O-antigen bactericidal antibody titers than coupling to K37/39, and in comparable titers to conjugates bearing a larger number of saccharides. This study demonstrates that the conjugation site plays a role in determining the immunogenicity in mice and one single attachment point may be sufficient to induce high levels of bactericidal antibodies
carbohydrates, Salmonella, vaccines, vaccine, glycoconjugate, glycoconjugate vaccine, protein modification
Structure type: polymer chemical repeating unit
Location inside paper: p.13199, fig.1
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_127517,IEDB_130701,IEDB_135509,IEDB_135513,IEDB_135514,IEDB_135611,IEDB_136093,IEDB_136105,IEDB_136775,IEDB_136906,IEDB_137472,IEDB_137486,IEDB_141794,IEDB_142488,IEDB_144983,IEDB_144998,IEDB_146664,IEDB_151528,IEDB_152206,IEDB_153307,IEDB_190606,IEDB_225177,IEDB_885823,IEDB_983930,IEDB_983931,SB_192,SB_44,SB_67,SB_7,SB_72
Methods: ELISA, chemical synthesis, biological assays, serological methods, HPLC, SEC, conjugation, MALDI-TOF/TOF MS, LC-ESI-MS/MS
3D data: 3D data
Related record ID(s): 30977
NCBI Taxonomy refs (TaxIDs): 90371
Show glycosyltransferases
There is only one chemically distinct structure:
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(later renamed to: Salmonella enterica ssp. enterica sv. Typhimurium 2192)