Production of Neisseria meningitidis transferrin-binding protein B by recombinant Bordetella pertussis.
Neisseria meningitidis serogroup B infections are among the major causes of fulminant septicemia and meningitis, especially severe in young children, and no broad vaccine is available yet. Because of poor immunogenicity of the serogroup B capsule, many efforts are now devoted to the identification of protective protein antigens. Among those are PorA and, more recently, transferrin-binding protein B (TbpB). In this study, TbpB of N. meningitidis was genetically fused to the N-terminal domain of the Bordetella pertussis filamentous hemagglutinin (FHA), and the fha-tbpB hybrid gene was expressed in B. pertussis either as a plasmid-borne gene or as a single copy inserted into the chromosome. The hybrid protein was efficiently secreted by the recombinant strains, despite its large size, and was recognized by both anti-FHA and anti-TbpB antibodies. A single intranasal administration of recombinant virulent or pertussis-toxin-deficient, attenuated B. pertussis to mice resulted in the production of antigen-specific systemic immunoglobulin G (IgG), as well as local IgG and IgA. The anti-TbpB serum antibodies were of the IgG1, IgG2a, and IgG2b isotypes and were found to express complement-mediated bactericidal activity against N. meningitidis. These observations indicate that recombinant B. pertussis may be a promising vector for the development of a mucosal vaccine against serogroup B meningococci.
Coppens
I
I
Laboratoire de Microbiologie Génétique et Moléculaire, INSERM U447, Institut Pasteur de Lille, F-59019 Lille, France.
Alonso
S
S
Antoine
R
R
Jacob-Dubuisson
F
F
Renauld-Mongénie
G
G
Jacobs
E
E
Locht
C
C
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001886:Bordetella pertussis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism; D033862:Iron-Binding Proteins; D051379:Mice; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D033882:Transferrin-Binding Protein B; D033863:Transferrin-Binding Proteins; D010566:Virulence Factors, Bordetella
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D002352:Carrier Proteins; D006388:Hemagglutinins; D033862:Iron-Binding Proteins; D011993:Recombinant Fusion Proteins; D033882:Transferrin-Binding Protein B; D033863:Transferrin-Binding Proteins; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis