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Structural basis for cooperativity of human monoclonal antibodies to meningococcal factor H-binding protein.
- Source :
-
Communications biology [Commun Biol] 2019 Jun 26; Vol. 2, pp. 241. Date of Electronic Publication: 2019 Jun 26 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Monoclonal antibody (mAb) cooperativity is a phenomenon triggered when mAbs couples promote increased bactericidal killing compared to individual partners. Cooperativity has been deeply investigated among mAbs elicited by factor H-binding protein (fHbp), a Neisseria meningitidis surface-exposed lipoprotein and one of the key antigens included in both serogroup B meningococcus vaccine Bexsero and Trumenba. Here we report the structural and functional characterization of two cooperative mAbs pairs isolated from Bexsero vaccines. The 3D electron microscopy structures of the human mAb-fHbp-mAb cooperative complexes indicate that the angle formed between the antigen binding fragments (fAbs) assume regular angle and that fHbp is able to bind simultaneously and stably the cooperative mAbs pairs and human factor H (fH) in vitro. These findings shed light on molecular basis of the antibody-based mechanism of protection driven by simultaneous recognition of the different epitopes of the fHbp and underline that cooperativity is crucial in vaccine efficacy.<br />Competing Interests: Competing interestsAll authors have declared no competing financial interest but the following competing nonfinancial interests: I.F., M.G., F.G., D.D., W.P., M.S., and V.M. are employees of GSK group of companies. L.J.L. was an employee of GSK group of companies when the experiments were performed. L.J.L. reports a grant from the European Union FP7 Framework Programme (FP7-PEOPLE-2013-IEF, grant number 623168) during the conduct of the study. I.P. held a Novartis Academy Ph.D. fellowship at the University of Bologna. The other authors report no financial conflict of interest.
- Subjects :
- Antibodies, Monoclonal immunology
Blood Bactericidal Activity
Complement Factor H metabolism
Epitope Mapping
Humans
Meningococcal Vaccines immunology
Microscopy, Electron, Transmission
Surface Plasmon Resonance
Antibodies, Monoclonal chemistry
Antigens, Bacterial immunology
Bacterial Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 2
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 31263785
- Full Text :
- https://doi.org/10.1038/s42003-019-0493-4