Title :

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

Author(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]

Journal title :

Frontiers in Molecular Biosciences

Abbreviated title :

Front. Mol. Biosci.

Volume number :

8

Publisher :

Frontiers Media SA

Publication date :

2021-10-14

ISSN :

2296-889X

English keyword(s) :

structural glycobiology
glycoconjugates
vaccines
Neisseria meningitidis
capsular polysaccharide

HAL domain(s) :

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

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

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

Research team(s) :

Computational Molecular Systems Biology

Submission date :

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