Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: meningitis [ICD11:
1D01 
];
infection due to Neisseria meningitidis [ICD11:
XN1DV ]
The structure was elucidated in this paperNCBI PubMed ID: 33158970Publication DOI: 10.1073/pnas.2011385117Journal NLM ID: 7505876Publisher: National Academy of Sciences
Correspondence: rino.r.rappuoli
gsk.com; roberto.x.adamo
gsk.com
Institutions: Instituto de Medicina Molecular Joгo Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal, Research and Development Centre, GlaxoSmithKline (GSK), 53100 Siena, Italy, Chemical Glycobiology Lab CIC bioGUNE Technology Park, 48160 Derio, Spain, Department of Chemistry, University of Cambridge, CB2 1EW Cambridge, United Kingdom, Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Bizkaia, Spain, and Department of Organic Chemistry II, University of the Basque Country, Universidad del Paнs Vasco/Euskal Herriko Unibertsitatea, 48940 Leioa, Bizkaia, Spain
Meningococcal meningitis remains a substantial cause of mortality and morbidity worldwide. Until recently, countries in the African meningitis belt were susceptible to devastating outbreaks, largely attributed to serogroup A Neisseria meningitidis (MenA). Vaccination with glycoconjugates of MenA capsular polysaccharide led to an almost complete elimination of MenA clinical cases. To understand the molecular basis of vaccine-induced protection, we generated a panel of oligosaccharide fragments of different lengths and tested them with polyclonal and monoclonal antibodies by inhibition enzyme-linked immunosorbent assay, surface plasmon resonance, and competitive human serum bactericidal assay, which is a surrogate for protection. The epitope was shown to optimize between three and six repeating units and to be O-acetylated. The molecular interactions between a protective monoclonal antibody and a MenA capsular polysaccharide fragment were further elucidated at the atomic level by saturation transfer difference NMR spectroscopy and X-ray crystallography. The epitope consists of a trisaccharide anchored to the antibody via the O- and N-acetyl moieties through either H-bonding or CH–p interactions. In silico docking showed that 3-O-acetylation of the upstream residue is essential for antibody binding, while O-acetate could be equally accommodated at three and four positions of the other two residues. These results shed light on the mechanism of action of current MenA vaccines and provide a foundation for the rational design of improved therapies.
carbohydrates, Neisseria meningitidis, vaccines, Structural glycobiology
Structure type: oligomer
Location inside paper: p.29796, Fig.1A, Fig.2B, Scheme S1, Biotin-MenA OS
Compound class: CPS
Contained glycoepitopes: IEDB_1330666,IEDB_1330667,IEDB_1330669,IEDB_1330671,IEDB_149549,IEDB_149550,IEDB_149551,IEDB_149552
Methods: 1H NMR, X-ray, ELISA, 31P NMR, MD simulations, de-O-acetylation, serological methods, STD NMR, SPR, conjugation
3D data: molecular modeling
NCBI Taxonomy refs (TaxIDs): 65699
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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