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Journal articles
Characterization of functional oligosaccharide mimics of the Shigella flexneri serotype 2a O-antigen: implications for the development of a chemically defined glycoconjugate vaccine.
Abstract : Protection against reinfection with noncapsulated Gram-negative bacteria, such as Shigella, an enteroinvasive bacterium responsible for bacillary dysentery, is mainly achieved by Abs specific for the O-Ag, the polysaccharide part of the LPS, the major bacterial surface Ag. The use of chemically defined glycoconjugates encompassing oligosaccharides mimicking the protective determinants carried by the O-Ag, thus expected to induce an efficient anti-LPS Ab response, has been considered an alternative to detoxified LPS-protein conjugate vaccines. The aim of this study was to identify such functional oligosaccharide mimics of the S. flexneri serotype 2a O-Ag. Using protective murine mAbs specific for S. flexneri serotype 2a and synthetic oligosaccharides designed to analyze the contribution of each sugar residue of the branched pentasaccharide repeating unit of the O-Ag, we demonstrated that the O-Ag exhibited an immunodominant serotype-specific determinant. We also showed that elongating the oligosaccharide sequence improved Ab recognition. From these antigenicity data, selected synthetic oligosaccharides were assessed for their potential to mimic the O-Ag by analyzing their immunogenicity in mice when coupled to tetanus toxoid via single point attachment. Our results demonstrated that induction of an efficient serotype 2a-specific anti-O-Ag Ab response was dependent on the length of the oligosaccharide sequence. A pentadecasaccharide representing three biological repeating units was identified as a potential candidate for further development of a chemically defined glycoconjugate vaccine against S. flexneri 2a infection.
Cited literature [72 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-00166117
Contributor : Sylvie Pochet Connect in order to contact the contributor
Submitted on : Wednesday, August 1, 2007 - 10:48:42 AM
Last modification on : Tuesday, October 19, 2021 - 10:25:51 PM
Long-term archiving on: : Friday, November 25, 2016 - 7:11:18 PM
Contributor : Sylvie Pochet Connect in order to contact the contributor
Submitted on : Wednesday, August 1, 2007 - 10:48:42 AM
Last modification on : Tuesday, October 19, 2021 - 10:25:51 PM
Long-term archiving on: : Friday, November 25, 2016 - 7:11:18 PM