Characterization of Functional Oligosaccharide Mimics of the Shigella Flexneri Serotype 2a O-antigen: Implications for the Development of a Chemically Defined Glycoconjugate Vaccine.
From: Unité de Pathogénie Microbienne Moléculaire, Institut National de la Santé et de la Recherche Médicale Unité 389. phalipon@pasteur.fr
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Feb 2006
- ISSN: 0022-1767
- Volume: 176
- Issue: 3
- Pages: 1686-94
- Medium: Print
- Language: English
- Citation (JAMA): Phalipon Armelle, Costachel Corina, Grandjean Cyrille, et al. Characterization of Functional Oligosaccharide Mimics of the Shigella Flexneri Serotype 2a O-antigen: Implications for the Development of a Chemically Defined Glycoconjugate Vaccine.. J. Immunol. Feb 2006;176:1686-94
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.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Carbohydrate Sequence, Drug Design, Dysentery, Bacillary, Glycoconjugates, Immunoglobulin G, Mice, Mice, Inbred BALB C, Molecular Mimicry, Molecular Sequence Data, O Antigens, Oligosaccharides, Serotyping, Shigella Vaccines, Shigella flexneri, Vaccines, Conjugate
Check for Full Text / PubMed Unique Identifier (PMID): 16424198
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