The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies.
GNA 1870 is a novel surface-exposed lipoprotein, identified by genome analysis of Neisseria meningitidis strain MC58, which induces bactericidal antibodies. Three sequence variants of the protein were shown to be sufficient to induce bactericidal antibodies against a panel of strains representative of the diversity of serogroup B meningococci. Here, we studied the antigenic and immunogenic properties of GNA 1870, which for convenience was divided into domains A, B, and C. The immune responses of mice immunized with each of the three variants were tested using overlapping peptides scanning the entire protein length and using recombinant fragments. We found that while most of the linear epitopes are located in the A domain, the bactericidal antibodies are directed against conformational epitopes located in the BC domain. This was also confirmed by the isolation of a bactericidal murine monoclonal antibody, which failed to recognize linear peptides on the A, B, and C domains separately but recognized a conformational epitope formed only by the combination of the B and C domains. Arginine in position 204 was identified as important for binding of the monoclonal antibody. The identification of the region containing bactericidal epitopes is an important step in the design of new vaccines against meningococci.
Giuliani
Marzia Monica
MM
IRIS, Chiron Vaccines, via Fiorentina 1, 53100 Siena, Italy. rino_rappuoli@chiron.com
Santini
Laura
L
Brunelli
Brunella
B
Biolchi
Alessia
A
Aricò
Beatrice
B
Di Marcello
Federica
F
Cartocci
Elena
E
Comanducci
Maurizio
M
Masignani
Vega
V
Lozzi
Luisa
L
Savino
Silvana
S
Scarselli
Maria
M
Rappuoli
Rino
R
Pizza
Mariagrazia
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D010446:Peptide Fragments; C488465:antigen 1870, Neisseria meningitidis