Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Host organism: Homo sapiens
Associated disease: septicemia [ICD11:
MA15.Y 
];
meningitis [ICD11:
1D01 ];
otitis media [ICD11:
AB0Z ];
infection due to Streptococcus pneumoniae [ICD11:
XN3PW ]
NCBI PubMed ID: 28945368Publication DOI: 10.1021/jacs.7b07836Journal NLM ID: 7503056Publisher: American Chemical Society
Correspondence: peter.seeberger
mpikg.mpg.de; claney.pereira
vaxxilon.com
Institutions: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany, Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany, Department of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, D-14195 Berlin, Germany
Invasive pneumococcal diseases (IPDs) remain the leading cause of vaccine-preventable childhood death, even though highly effective pneumococcal conjugate vaccines (PCVs) are used in national immunization programs in many developing countries. Licensed PCVs currently cover only 13 of the over 90 serotypes of Streptococcus pneumoniae (Sp), so nonvaccine serotypes are a major obstacle to the effective control of IPD. Sp serotype 2 (ST2) is such a nonvaccine serotype that is the main cause of IPD in many countries, including Nepal, Bangladesh, and Guatemala. Glycoconjugate vaccines based on synthetic oligosaccharides instead of isolated polysaccharides offer an attractive alternative to the traditional process for PCV development. To prevent the IPDs caused by ST2, we identified an effective ST2 neoglycoconjugate vaccine candidate that was identified using a medicinal chemistry approach. Glycan microarrays containing a series of synthetic glycans resembling portions of the ST2 capsular polysaccharide (CPS) repeating unit were used to screen human and rabbit sera and identify epitope hits. Synthetic hexasaccharide 2, resembling one repeating unit (RU) of ST2 CPS, emerged as a hit from the glycan array screens. Vaccination with neoglycoconjugates consisting of hexasaccharide 2 coupled to carrier protein CRM197 stimulates a T-cell-dependent B-cell response that induced CPS-specific opsonic antibodies in mice, resulting in killing of encapsulated bacteria by phagocytic activity. Subcutaneous immunization with neoglycoconjugate protected mice from transnasal challenge with the highly virulent ST2 strain NCTC 7466 by reducing the bacterial load in lung tissue and blood.
capsular polysaccharide, glycoconjugate vaccines, chemical synthesis, Glycan arrays, Streptococcus pneumoniae Type 2
Structure type: polymer chemical repeating unit
Location inside paper: p.14784, fig.1
Trivial name: capsule type 2
Compound class: CPS, EPS, polysaccharide, rhamnoglucan
Contained glycoepitopes: IEDB_115136,IEDB_136105,IEDB_140630,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_225177,IEDB_885823,IEDB_983931,SB_192
Methods: 13C NMR, 1H NMR, NMR-2D, IR, SDS-PAGE, TLC, ELISA, chemical synthesis, MALDI-TOF MS, biological assays, optical rotation measurement, statistical analysis, immunization, conjugation, HR-ESI-MS, flow cytometry, microarray binding assays
Comments, role: published polymerization frame was shifted for consistency with other records
Related record ID(s): 12413
NCBI Taxonomy refs (TaxIDs): 1313Reference(s) to other database(s): GTC:G67978MJ, GlycomeDB:
25030
Show glycosyltransferases
There is only one chemically distinct structure:
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