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: 19201878Publication DOI: 10.4049/jimmunol.0803141Journal NLM ID: 2985117RPublisher: Bethesda, MD: American Association of Immunologists
Correspondence: laurence.mulard

pasteur.fr
Institutions: Institut Pasteur, Unite de Pathogenie Microbienne Moleculaire, Paris, France
The protective Ag of Shigella, the Gram-negative enteroinvasive bacterium causing bacillary dysentery, or shigellosis, is its O-specific polysaccharide (O-SP) domain of the LPS, the major bacterial surface component. As an alternative to the development of detoxified LPS-based conjugate vaccines, recent effort was put into the investigation of neoglycoproteins encompassing synthetic oligosaccharides mimicking the protective Ags of the O-SP. We previously reported that when coupled to tetanus toxoid via single point attachment, a synthetic pentadecasaccharide representing three biological repeating units of the O-SP of Shigella flexneri 2a (SF2a), one of the most common Shigella serotypes, elicits a better serum anti-LPS 2a Ab response in mice than shorter synthetic O-SP sequences. In this study, we show that the pentadecasaccharide-induced anti-LPS 2a Abs protect passively administered naive mice from Shigella infection. Therefore, this three repeating units sequence, which is recognized by anti-SF2a sera from infected patients, acts as a functional mimic of the native polysaccharide Ag. Analyses of parameters influencing immunogenicity revealed that an investigational SF2a vaccine displaying a pentadecasaccharide:tetanus toxoid molar loading of 14:1 triggers a high and sustained anti-LPS Ab response, without inducing anti-linker Ab, when administered four times at a dose corresponding to 1 mug of carbohydrate. In addition, the profile of the anti-LPS Ab response, dominated by IgG1 production (Th2-type response), mimics that observed in human upon natural SF2a infection. This synthetic carbohydrate-based conjugate may be a candidate for a SF2a vaccine
O-specific polysaccharide, vaccines, conjugate vaccines, synthetic oligosaccharides, Shigella flexneri 2a, shigellosis
Structure type: polymer chemical repeating unit
Location inside paper: p.2242, fig.1
Trivial name: biological repeating unit
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_125613,IEDB_125614,IEDB_127514,IEDB_130687,IEDB_133752,IEDB_133753,IEDB_133754,IEDB_135806,IEDB_135807,IEDB_135808,IEDB_135809,IEDB_135813,IEDB_135817,IEDB_135849,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_141815,IEDB_141816,IEDB_142488,IEDB_143253,IEDB_144998,IEDB_146664,IEDB_151531,IEDB_153213,IEDB_225177,IEDB_885823,IEDB_983931,SB_192
Methods: serological methods
Biological activity: serological data
Related record ID(s): 1253, 3877, 9582, 20186, 22751, 23858, 23908, 23966
NCBI Taxonomy refs (TaxIDs): 42897Reference(s) to other database(s): GTC:G13476UX, GlycomeDB:
25371
Show glycosyltransferases
There is only one chemically distinct structure: