7oo2 | pdb_00007oo2
Crystal structure of an antibody targeting the capsular polysaccharide of serogroup X Neisseria meningitidis (MenX)
Structural highlights
Publication Abstract from PubMedDespite the considerable progress toward the eradication of meningococcal disease with the introduction of glycoconjugate vaccines, previously unremarkable serogroup X has emerged in recent years, recording several outbreaks throughout the African continent. Different serogroup X polysaccharide-based vaccines have been tested in preclinical trials, establishing the principles for further improvement. To elucidate the antigenic determinants of the MenX capsular polysaccharide, we generated a monoclonal antibody, and its bactericidal nature was confirmed using the rabbit serum bactericidal assay. The antibody was tested by the inhibition enzyme-linked immunosorbent assay and surface plasmon resonance against a set of oligosaccharide fragments of different lengths. The epitope was shown to be contained within five to six alpha-(1-4) phosphodiester mannosamine repeating units. The molecular interactions between the protective monoclonal antibody and the MenX capsular polysaccharide fragment were further detailed at the atomic level by saturation transfer difference nuclear magnetic resonance (NMR) spectroscopy. The NMR results were used for validation of the in silico docking analysis between the X-ray crystal structure of the antibody (Fab fragment) and the modeled hexamer oligosaccharide. The antibody recognizes the MenX fragment by binding all six repeating units of the oligosaccharide via hydrogen bonding, salt bridges, and hydrophobic interactions. In vivo studies demonstrated that conjugates containing five to six repeating units can produce high functional antibody levels. These results provide an insight into the molecular basis of MenX vaccine-induced protection and highlight the requirements for the epitope-based vaccine design. Elucidating the Structural and Minimal Protective Epitope of the Serogroup X Meningococcal Capsular Polysaccharide.,Pietri GP, Tontini M, Brogioni B, Oldrini D, Robakiewicz S, Henriques P, Calloni I, Abramova V, Santini L, Malic S, Miklic K, Lisnic B, Bertuzzi S, Unione L, Balducci E, de Ruyck J, Romano MR, Jimenez-Barbero J, Bouckaert J, Jonjic S, Rovis TL, Adamo R Front Mol Biosci. 2021 Oct 14;8:745360. doi: 10.3389/fmolb.2021.745360. , eCollection 2021. PMID:34722634[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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