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

Agnese Faleri, Laura Santini, Sébastien Brier, Werner Pansegrau, Paola Lo Surdo, Maria Scarselli, Francesca Buricchi, Gianfranco Volpini, Alessia Genovese, Stijn van der Veen, Susan Lea, Christoph M. Tang, Silvana Savino, Mariagrazia Pizza, Oretta Finco, Nathalie Norais, Vega Masignani

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30 Citations (Scopus)

Abstract

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 languageEnglish
Pages (from-to)1644-1653
Number of pages10
JournalThe FASEB Journal
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 2014
Externally publishedYes

Keywords

  • Hydrogen/deuterium exchange mass spectrometry
  • MAb synergy
  • MenB vaccine
  • Meningococcal antigen

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