8S6E

Monoclonal antibody MenW targeting serogroup W of Neisseria meningitidis

Summary for 8S6E

• Entry DOI: 10.2210/pdb8s6e/pdb
• Descriptor: MenW.01 Heavy chain, MenW.01 Light chain, SODIUM ION, ... (4 entities in total)
• Functional Keywords: immune system, antibody, menw
• Biological source: Mus musculus; More
• Total number of polymer chains: 2
• Total formula weight: 48023.37

Authors

Pietri, G.P.,Bertuzzi, S.,Karnicar, K.,Unione, L.,Lisnic, B.,Malic, S.,Miklic, K.,Novak, M.,Calloni, I.,Santini, L.,Usenik, A.,Rosaria Romano, M.,Adamo, R.,Jonjic, S.,Turk, D.,Jimenez-Barbero, J.,Lenac Rovis, T. (deposition date: 2024-02-27, release date: 2024-06-26, Last modification date: 2024-10-16)

Primary citation

Pietri, G.P.,Bertuzzi, S.,Karnicar, K.,Unione, L.,Lisnic, B.,Malic, S.,Miklic, K.,Novak, M.,Calloni, I.,Santini, L.,Usenik, A.,Romano, M.R.,Adamo, R.,Jonjic, S.,Turk, D.,Jimenez-Barbero, J.,Lenac Rovis, T.
Antigenic determinants driving serogroup-specific antibody response to Neisseria meningitidis C, W, and Y capsular polysaccharides: Insights for rational vaccine design.
Carbohydr Polym, 341:122349-122349, 2024

PubMed Abstract: Meningococcal glycoconjugate vaccines sourced from capsular polysaccharides (CPSs) of pathogenic Neisseria meningitidis strains are well-established measures to prevent meningococcal disease. However, the exact structural factors responsible for antibody recognition are not known. CPSs of Neisseria meningitidis serogroups Y and W differ by a single stereochemical center, yet they evoke specific immune responses. Herein, we developed specific monoclonal antibodies (mAbs) targeting serogroups C, Y, and W and evaluated their ability to kill bacteria. We then used these mAbs to dissect structural elements responsible for carbohydrate-protein interactions. First, Men oligosaccharides were screened against the mAbs using ELISA to select putative lengths representing the minimal antigenic determinant. Next, molecular interaction features between the mAbs and serogroup-specific sugar fragments were elucidated using STD-NMR. Moreover, X-ray diffraction data with the anti-MenW CPS mAb enabled the elucidation of the sugar-antibody binding mode. Our findings revealed common traits in the epitopes of all three sialylated serogroups. The minimal binding epitopes typically comprise five to six repeating units. Moreover, the O-acetylation of the neuraminic acid moieties was fundamental for mAb binding. These insights hold promise for the rational design of optimized meningococcal oligosaccharides, opening new avenues for novel production methods, including chemical or enzymatic approaches.

PubMed: 38876728
DOI: 10.1016/j.carbpol.2024.122349

Experimental method

X-RAY DIFFRACTION (1.95 Å)