Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective immunity in humans.
GNA2132 is a Neisseria meningitidis antigen of unknown function, discovered by reverse vaccinology, which has been shown to induce bactericidal antibodies in animal models. Here we show that this antigen induces protective immunity in humans and it is recognized by sera of patients after meningococcal disease. The protein binds heparin in vitro through an Arg-rich region and this property correlates with increased survival of the unencapsulated bacterium in human serum. Furthermore, two proteases, the meningococcal NalP and human lactoferrin, cleave the protein upstream and downstream from the Arg-rich region, respectively. We conclude that GNA2132 is an important protective antigen of N. meningitidis and we propose to rename it, Neisserial Heparin Binding Antigen (NHBA).
Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
Davide
D
Serruto
Tiziana
T
Spadafina
Laura
L
Ciucchi
Lisa A
LA
Lewis
Sanjay
S
Ram
Marta
M
Tontini
Laura
L
Santini
Alessia
A
Biolchi
Kate L
KL
Seib
Marzia M
MM
Giuliani
John J
JJ
Donnelly
Francesco
F
Berti
Silvana
S
Savino
Maria
M
Scarselli
Paolo
P
Costantino
J Simon
JS
Kroll
Clíona
C
O'Dwyer
Jiazhou
J
Qiu
Andrew G
AG
Plaut
Richard
R
Moxon
Rino
R
Rappuoli
Mariagrazia
M
Pizza
Beatrice
B
Aricò
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology* / Q000472:pathogenicity; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
C062991:AZU1 protein, human; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D022401:Meningococcal Vaccines; D037521:Virulence Factors; D007781:Lactoferrin