title: Epitope mapping of a bactericidal monoclonal antibody against the factor H binding protein of Neisseria meningitidis.
abstract: The factor H binding protein (fHbp) is a 27-kDa membrane-anchored lipoprotein of Neisseria meningitidis that allows the survival of the bacterium in human plasma; it is also a major component of a universal vaccine against meningococcus B. In this study, we used nuclear magnetic resonance spectroscopy, mutagenesis, and in silico modeling to map the epitope recognized by MAb502, a bactericidal monoclonal antibody elicited by fHbp. The data show that the antibody recognizes a conformational epitope within a well-defined area of the immunodominant C-terminal domain of the protein that is formed by two loops connecting different beta-strands of a beta-barrel and a short alpha-helix brought in spatial proximity by the protein folding. The identification of the protective epitopes of fHbp is an important factor for understanding the mechanism(s) of an effective immune response and provides valuable guidelines for designing variants of the protein able to induce broadly protective immunity.
authors.affiliation: Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Scarselli
authors.forename: Francesca
authors.initials: F
authors.lastname: Cantini
authors.forename: Laura
authors.initials: L
authors.lastname: Santini
authors.forename: Daniele
authors.initials: D
authors.lastname: Veggi
authors.forename: Sara
authors.initials: S
authors.lastname: Dragonetti
authors.forename: Claudio
authors.initials: C
authors.lastname: Donati
authors.forename: Silvana
authors.initials: S
authors.lastname: Savino
authors.forename: Marzia M
authors.initials: MM
authors.lastname: Giuliani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Comanducci
authors.forename: Federica
authors.initials: F
authors.lastname: Di Marcello
authors.forename: Giacomo
authors.initials: G
authors.lastname: Romagnoli
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
mesh_terms: D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000737:chemistry* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology*; D018604:Epitope Mapping; D008589:Meningococcal Infections / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C484699:factor H-binding protein, Neisseria meningitidis