{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:25:06Z","timestamp":1791095106674,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u03bcg 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.<\/jats:p>","DOI":"10.4049\/jimmunol.0803141","type":"journal-article","created":{"date-parts":[[2009,2,9]],"date-time":"2009-02-09T12:02:33Z","timestamp":1234180953000},"page":"2241-2247","source":"Crossref","is-referenced-by-count":128,"title":["A Synthetic Carbohydrate-Protein Conjugate Vaccine Candidate against\n                    <i>Shigella flexneri<\/i>\n                    2a Infection"],"prefix":"10.1093","volume":"182","author":[{"given":"Armelle","family":"Phalipon","sequence":"first","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 de Pathog\u00e9nie Microbienne Mol\u00e9culaire , Paris,","place":["France"]},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Institut Pasteur, Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Tanguy","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 de Pathog\u00e9nie Microbienne Mol\u00e9culaire , Paris,","place":["France"]},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Institut Pasteur, Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrille","family":"Grandjean","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 de Chimie Organique , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 de Chimie Organique , Paris,","place":["France"]},{"name":"Institut Pasteur, Unit\u00e9 de Chimie des Biomol\u00e9cules , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"B\u00e9lot","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 de Chimie Organique , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe J","family":"Sansonetti","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 de Pathog\u00e9nie Microbienne Mol\u00e9culaire , Paris,","place":["France"]},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Institut Pasteur, Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence A","family":"Mulard","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 de Chimie Organique , Paris,","place":["France"]},{"name":"Institut Pasteur, Unit\u00e9 de Chimie des Biomol\u00e9cules , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,2,15]]},"reference":[{"key":"2026012806245376400_R1","first-page":"293","article-title":"Vaccines based on the cell surface carbohydrates of pathogenic bacteria.","volume-title":"An. 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Dis.","year":"1997"},{"key":"2026012806245376400_R19","first-page":"155","article-title":"Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults.","volume-title":"Lancet","year":"1997"},{"key":"2026012806245376400_R20","first-page":"701","article-title":"Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2a-rEPAsucc conjugate vaccines in one- to four-year-old children.","volume-title":"Pediatr. Infect. Dis. J.","year":"2003"},{"key":"2026012806245376400_R21","first-page":"849","article-title":"Synthesis of the methyl glycosides of a di- and two trisaccharide fragments specific for the Shigella flexneri serotype 2a O-antigen.","volume-title":"J. Carbohydr. 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Chem.","year":"2000"},{"key":"2026012806245376400_R23","first-page":"2211","article-title":"Convergent synthesis of the methyl glycosides of a tetra- and a pentasaccharide fragment of the Shigella flexneri serotype 2a O-specific polysaccharide.","volume-title":"Tetrahedron Asymmetry","year":"2002"},{"key":"2026012806245376400_R24","first-page":"2475","article-title":"Total synthesis of a tetra- and two pentasaccharide fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a.","volume-title":"Tetrahedron","year":"2004"},{"key":"2026012806245376400_R25","first-page":"8215","article-title":"Synthesis of the methyl glycoside of a branched octasaccharide fragment specific for the Shigella flexneri serotype 2a O-antigen.","volume-title":"Tetrahedron Lett.","year":"2002"},{"key":"2026012806245376400_R26","first-page":"1060","article-title":"Blockwise approach to fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a: convergent synthesis of a decasaccharide representative of a dimer of the branched repeating unit.","volume-title":"J. 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