Epitopes described in "Characterization of functional oligosaccharide mimics of the Shigella flexneri serotype 2a O-antigen: implications for the development of a chemically defined glycoconjugate vaccine."

Reference
Article Authors:Armelle Phalipon; Corina Costachel; Cyrille Grandjean; Audrey Thuizat; Catherine Guerreiro; Myriam Tanguy; Farida Nato; Brigitte Vulliez-Le Normand; Frédéric Bélot; Karen Wright; Véronique Marcel-Peyre; Philippe J Sansonetti; Laurence A Mulard
Article Title:Characterization of functional oligosaccharide mimics of the Shigella flexneri serotype 2a O-antigen: implications for the development of a chemically defined glycoconjugate vaccine.
Reference Detail
Reference ID:1018837
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.
Affiliations:Unité de Pathogénie Microbienne Moléculaire, Institut National de la Santé et de la Recherche Médicale Unité 389. phalipon@pasteur.fr
Date:2006
Reference Type:Literature
PubMed ID:16424198
Journal:J Immunol
Journal Volume:176
Article Pages:1686-94
Journal ISSN:0022-1767
Article Chemical List:Glycoconjugates;Immunoglobulin G;O Antigens;Oligosaccharides;Shigella Vaccines;Vaccines, Conjugate
Article MeSH List:Amino Acid Sequence; Animals; Carbohydrate Sequence; Drug Design; Dysentery, Bacillary(immunology; prevention & control); Glycoconjugates(chemistry; immunology); Immunoglobulin G(genetics); Mice; Mice, Inbred BALB C; Molecular Mimicry(immunology); Molecular Sequence Data; O Antigens(chemistry; immunology); Oligosaccharides(chemistry; immunology); Serotyping; Shigella Vaccines(chemical synthesis; immunology); Shigella flexneri(chemistry; classification; immunology); Vaccines, Conjugate(chemistry; immunology)
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