Epitope mapping of a bactericidal monoclonal antibody against the factor H binding protein of Neisseria meningitidis.
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.
Scarselli
Maria
M
Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy.
Cantini
Francesca
F
Santini
Laura
L
Veggi
Daniele
D
Dragonetti
Sara
S
Donati
Claudio
C
Savino
Silvana
S
Giuliani
Marzia M
MM
Comanducci
Maurizio
M
Di Marcello
Federica
F
Romagnoli
Giacomo
G
Pizza
Mariagrazia
M
Banci
Lucia
L
Rappuoli
Rino
R
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
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C484699:factor H-binding protein, Neisseria meningitidis