Titre :

Elucidating the Structural and Minimal Protective Epitope of the Serogroup X Meningococcal Capsular Polysaccharide

Auteur(s) :

Pietri, Gian Pietro [Auteur]
Tontini, Marta [Auteur]
Brogioni, Barbara [Auteur]
Oldrini, Davide [Auteur]
Robakiewicz, Stefania [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Henriques, Pedro [Auteur]
Calloni, Ilaria [Auteur]
Abramova, Vera [Auteur]
Santini, Laura [Auteur]
Malić, Suzana [Auteur]
Miklić, Karmela [Auteur]
Lisnic, Berislav [Auteur]
Bertuzzi, Sara [Auteur]
Unione, Luca [Auteur]
Balducci, Evita [Auteur]
De Ruyck, Jerome [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Romano, Maria Rosaria [Auteur]
Jimenez-Barbero, Jesus [Auteur]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Jonjic, Stipan [Auteur]
Rovis, Tihana Lenac [Auteur]
Adamo, Roberto [Auteur]

Titre de la revue :

Frontiers in Molecular Biosciences

Nom court de la revue :

Front. Mol. Biosci.

Numéro :

8

Éditeur :

Frontiers Media SA

Date de publication :

2021-10-14

ISSN :

2296-889X

Mot(s)-clé(s) en anglais :

structural glycobiology
glycoconjugates
vaccines
Neisseria meningitidis
capsular polysaccharide

Discipline(s) HAL :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Despite 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 ...
Lire la suite >Despite 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 α-(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.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Computational Molecular Systems Biology

Date de dépôt :

2021-10-14T13:12:05Z
2021-10-18T07:47:48Z
2022-10-21T14:47:57Z
2022-11-08T09:41:59Z