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Structure type: polymer biological repeating unit
Compound class: O-polysaccharide
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_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

• Article ID: 3594
  Pozsgay V "Recent developments in synthetic oligosaccharide-based bacterial vaccines" - Current Topics in Medicinal Chemistry 8(2) (2008) 126-140
  

  Synthetic advances made possible chemical assembly of complex oligosaccharide fragments of polysaccharide domains on the surface of human pathogenic bacteria. These oligosaccharides may be recognized by antibodies raised against high molecular weight, native, polysaccharides. In addition to their antigenicity, synthetic oligosaccharides can also function as haptens in their protein conjugates that can elicit not only oligo- but also polysaccharide-specific IgG antibodies in animal models and in humans. A major milestone in the development of new generation vaccines was the demonstration that protein conjugates of synthetic fragments of the capsular polysaccharide of Haemophilus influenzae type b are as efficacious in preventing childhood meningitis and other diseases as is the corresponding licensed commercial vaccine containing the bacterial polysaccharide. The lessons learnt in this and other endeavors described herein are manifold. For example, they teach us about the significance of the oligosaccharide epitope size, the number of their copies per protein in the conjugate, the possible effect of the spacer on anti-saccharide immune response, and the proper choice of the carrier protein combined with the selection of the animal model. The H. influenzae b story also teaches us that that the synthetic approach can be commercially viable.

  Haemophilus influenzae, Streptococcus pneumoniae, Oligosaccharides, Shigella dysenteriae type 1, keyhole limpet hemocyanin, keyhole limpet hemocyanine

  NCBI PubMed ID: 18289082
  Journal NLM ID: 101119673
  Publisher: Bentham Science Publishers
  Correspondence: pozsgayv@mail.nih.gov
  Institutions: National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Dr., MSC 2423, Bethesda, MD 20892-2423, USA
  Methods: chemical synthesis
  
   
  
  Shigella flexneri 2a
  CSDB ID 23492 (all data & tools)
• Article ID: 5760
  Dobrochaeva K, Khasbiulina N, Shilova N, Antipova N, Obukhova P, Galanina O, Blixt O, Kunz H, Filatov A, Knirel Y, Le Pendu J, Khaidukov S, Bovin N "Specificity of human natural antibodies referred to as anti-Tn" - Molecular Immunology 120 (2020) 74-82
  

  To understand the role of human natural IgM known as antibodies against the carbohydrate epitope Tn, the antibodies were isolated using GalNAcα-Sepharose affinity chromatography, and their specificity was profiled using microarrays (a glycan array printed with oligosaccharides and bacterial polysaccharides, as well as a glycopeptide array), flow cytometry, and inhibition ELISA. The antibodies bound a restricted number of GalNAcα-terminated oligosaccharides better than the parent monosaccharide, e.g., 6-O-Su-GalNAcα and GalNAcα1-3Galβ1-3(4)GlcNAcβ. The binding with several bacterial polysaccharides that have no structural resemblance to the affinity ligand GalNAcα was quite unexpected. Given that GalNAcα is considered the key fragment of the Tn antigen, it is surprising that these antibodies bind weakly GalNAcα-OSer and do not bind a wide variety of GalNAcα-OSer/Thr-containing mucin glycopeptides. At the same time, we have observed specific binding to cells having Tn-positive glycoproteins containing similar glycopeptide motifs in a conformationally rigid macromolecule. Thus, specific recognition of the Tn antigen apparently requires that the naturally occurring "anti-Tn" IgM recognize a complex epitope comprising the GalNAcα as an essential component and a fairly long amino acid sequence where the amino acids adjacent to GalNAcα do not contact the antibody paratope; i.e., the antibodies recognize a spatial epitope or a molecular pattern rather than a classical continuous sequence. In addition, we have not found any increase in the binding of natural antibodies when GalNAcα residues were clustered. These results may help in further development of anticancer vaccines based on synthetic Tn constructs.

  cancer, glycans, natural antibodies, anti-glycan antibodies, Tn antigen

  NCBI PubMed ID: 32087569
  Publication DOI: 10.1016/j.molimm.2020.02.005
  Journal NLM ID: 7905289
  Publisher: Elsevier
  Correspondence: professorbovin@yandex.ru
  Institutions: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, Russian Federation, Semiotik LLC, 16/10 Miklukho-Maklaya, Moscow, Russian Federation, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, Russian Federation, National Research University Higher School of Economics, Moscow, Russian Federation, Department of Chemistry, Chemical Biology, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark, Institut Fur Organische Chemie, Johannes Gutenberg-Universitat Mainz, Duesbergweg 10-14, D-55128, Mainz, Germany, Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russian Federation, University of Nantes, Inserm, U892 IRT UN, 8 Quai MonCousu, BP70721 Nantes, FR 44007, France
  Methods: ELISA, affinity chromatography, flow cytometry analysis, printed glycan array (PGA) analysis, FACS assay
  
   
  
  Shigella flexneri 2a
  CSDB ID 3994 (all data & tools)