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Factor H binding protein (fHbp) is one of the main antigens of the 4-component meningococcus B (4CMenB) multicomponent vaccine against disease caused by serogroup B Neisseria meningitidis (MenB). fHbp binds the complement down-regulating protein human factor H (hfH), thus resulting in immune evasion. fHbp exists in 3 variant groups with limited cross-protective responses. Previous studies have described the generation of monoclonal antibodies (mAbs) targeting variant-specific regions of fHbp. Here we report for the first time the functional characterization of two mAbs that recognize a wide panel of fHbp variants and subvariants on the MenB surface and that are able to inhibit fHbp binding to hfH. The antigenic regions targeted by the two mAbs were accurately mapped by hydrogen-deuterium exchange mass spectrometry (HDX-MS), revealing partially overlapping epitopes on the N terminus of fHbp. Furthermore, while none of the mAbs had bactericidal activity on its own, a synergistic effect was observed for each of them when tested by the human complement serum bactericidal activity (hSBA) assay in combination with a second nonbactericidal mAb. The bases underlying fHbp variant cross-reactivity, as well as inhibition of hfH binding and cooperativity effect observed for the two mAbs, are discussed in light of the mapped epitopes.

Original publication

DOI

10.1096/fj.13-239012

Type

Journal article

Journal

FASEB J

Publication Date

04/2014

Volume

28

Pages

1644 - 1653

Keywords

MenB vaccine, hydrogen/deuterium exchange mass spectrometry, mAb synergy, meningococcal antigen, Antibodies, Monoclonal, Antigens, Bacterial, Bacterial Proteins, Complement Factor H, Cross Reactions, Deuterium Exchange Measurement, Epitope Mapping, Epitopes, Genetic Variation, Humans, Mass Spectrometry, Meningococcal Infections, Meningococcal Vaccines, Models, Molecular, Neisseria meningitidis, Serogroup B, Protein Binding, Protein Conformation, Surface Plasmon Resonance