NadA, a novel vaccine candidate of Neisseria meningitidis.
Neisseria meningitidis is a human pathogen, which, in spite of antibiotic therapy, is still a major cause of mortality due to sepsis and meningitis. Here we describe NadA, a novel surface antigen of N. meningitidis that is present in 52 out of 53 strains of hypervirulent lineages electrophoretic types (ET) ET37, ET5, and cluster A4. The gene is absent in the hypervirulent lineage III, in N. gonorrhoeae and in the commensal species N. lactamica and N. cinerea. The guanine/cytosine content, lower than the chromosome, suggests acquisition by horizontal gene transfer and subsequent limited evolution to generate three well-conserved alleles. NadA has a predicted molecular structure strikingly similar to a novel class of adhesins (YadA and UspA2), forms high molecular weight oligomers, and binds to epithelial cells in vitro supporting the hypothesis that NadA is important for host cell interaction. NadA induces strong bactericidal antibodies and is protective in the infant rat model suggesting that this protein may represent a novel antigen for a vaccine able to control meningococcal disease caused by three hypervirulent lineages.
Comanducci
Maurizio
M
Immunological Research Institute Siena, Chiron S.p.A., via Fiorentina 1, 53100 Siena, Italy.
Bambini
Stefania
S
Brunelli
Brunella
B
Adu-Bobie
Jeannette
J
Aricò
Beatrice
B
Capecchi
Barbara
B
Giuliani
Marzia Monica
MM
Masignani
Vega
V
Santini
Laura
L
Savino
Silvana
S
Granoff
Dan M
DM
Caugant
Dominique A
DA
Pizza
Mariagrazia
M
Rappuoli
Rino
R
Mora
Marirosa
M
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001482:Base Composition; D001483:Base Sequence; D015153:Blotting, Western; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D005434:Flow Cytometry; D022761:Gene Transfer, Horizontal / Q000235:genetics; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D051381:Rats
D000954:Antigens, Surface; D007106:Immune Sera; D022401:Meningococcal Vaccines; C458883:NMB 1994 antigen, rat