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).
Serruto
Davide
D
Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
Spadafina
Tiziana
T
Ciucchi
Laura
L
Lewis
Lisa A
LA
Ram
Sanjay
S
Tontini
Marta
M
Santini
Laura
L
Biolchi
Alessia
A
Seib
Kate L
KL
Giuliani
Marzia M
MM
Donnelly
John J
JJ
Berti
Francesco
F
Savino
Silvana
S
Scarselli
Maria
M
Costantino
Paolo
P
Kroll
J Simon
JS
O'Dwyer
Clíona
C
Qiu
Jiazhou
J
Plaut
Andrew G
AG
Moxon
Richard
R
Rappuoli
Rino
R
Pizza
Mariagrazia
M
Aricò
Beatrice
B
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