Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: bacillary dysentery (shigellosis) [ICD11:
1A02 
, ICD11:
SA56 , ICD11:
XN7HG ];
infection due to Shigella flexneri [ICD11:
XN7Y2 ]
NCBI PubMed ID: 26918643Publication DOI: 10.1021/acs.bioconjchem.5b00617Journal NLM ID: 9010319Publisher: Washington, DC: American Chemical Society
Correspondence: laurence.mulard
pasteur.fr
Institutions: CNRS UMR 3523, Institut Pasteur, F-75015 Paris, France, Institute for Translational Vaccinology (Intravacc), P.O. Box 450, 3720 AL Bilthoven, The Netherlands, Unite de Chimie des Biomolecules, Institut Pasteur, 28 rue du Dr Roux, 75 724 Paris Cedex 15, France, Unite de Pathogenie Microbienne Moleculaire, Institut Pasteur, 28 rue du Dr Roux, 75 724 Paris Cedex 15, France, INSERM U1202, Institut Pasteur, F75015 Paris, France
Conjugation chemistry is among the most important parameters governing the efficacy of glycoconjugate vaccines. High robustness is required to ensure high yields and batch to batch reproducibility. Herein, we have established a robust bioconjugation protocol based on the thiol-maleimide addition. Major variables were determined and acceptable margins were investigated for a synthetic pentadecasaccharide-tetanus toxoid conjugate, which is a promising vaccine candidate against Shigella flexneri serotype 2a infection. The optimized process is applicable to any thiol-equipped hapten and provides an efficient control of the hapten:carrier ratio. Moreover, comparison of four S. flexneri 2a glycoconjugates only differing by their pentadecasaccharide:tetanus toxoid ratio confirmed preliminary findings indicating that hapten loading is critical for immunogenicity with an optimal ratio here in the range of 17 +/- 5. In addition, the powerful influence of alum on the immunogenicity of a Shigella synthetic carbohydrate-based conjugate vaccine candidate is demonstrated for the first time, with a strong anti-S. flexneri 2a antibody response sustained for more than one year.
serotype, Shigella flexneri, antibodies, glycoconjugate vaccines, antibody response, vaccines, Synthetic, robust bioconjugation protocol
Structure type: polymer chemical repeating unit
Location inside paper: p.884
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_135813,IEDB_137340,IEDB_1394181,IEDB_141807,IEDB_142488,IEDB_144998,IEDB_145005,IEDB_145010,IEDB_146664,IEDB_151531,IEDB_983931,SB_192
Methods: 1H NMR, kinetics assays, serological methods, HPLC, HPSEC, statistical analysis, immunization, conjugation
Comments, role: The total degree of non-stoichiometric O-acetylation on RhaIII residues are ~ 90%.
NCBI Taxonomy refs (TaxIDs): 42897Reference(s) to other database(s): GTC:G38657UI
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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