Two cross-reactive monoclonal antibodies recognize overlapping epitopes on Neisseria meningitidis factor H binding protein but have different functional properties.

Journal article

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.

Authors: Faleri, A; Santini, L; Brier, S; Pansegrau, W; Lo Surdo, P

• Publication status: Published
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• Volume: 28
• Issue: 4
• Pages: 1644-1653
• Publication date: 2014-04-01
• DOI: 10.1096/fj.13-239012
• EISSN: 1530-6860
• ISSN: 0892-6638
• Language: English
• Keywords: Genetic Variation; Antibodies, Monoclonal; Protein Conformation; Bacterial Proteins; Complement Factor H; Surface Plasmon Resonance; Mass Spectrometry; Antigens, Bacterial; Humans; Neisseria meningitidis, Serogroup B; Cross Reactions; Deuterium Exchange Measurement; Meningococcal Vaccines; Models, Molecular; Epitope Mapping; Protein Binding; Epitopes; Meningococcal Infections