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 th e serogroup B capsule, many efforts are now devoted to the identification o f protective protein antigens. Among those are PorA and, more recently, tra nsferrin-binding protein B (TbpB). In this study, TbpB of N. meningitidis w as genetically fused to the N-terminal domain of the Bordetella pertussis f ilamentous hemagglutinin (FHA), and the fha-tbpB hybrid gene was expressed in A pertussis either as a plasmid-borne gene or as a single copy inserted into the chromosome. The hybrid protein was efficiently secreted by the rec ombinant strains, despite its large size, and was recognized by both anti-F HA and anti-TbpB antibodies. A single intranasal administration of recombin ant virulent or pertussis-toxin-deficient, attenuated B. pertussis to mice resulted in the production of antigen-specific systemic immunoglobulin G (I gG), as well as local IgG and IgA. The anti-TbpB serum antibodies were of t he IgG1, IgG2a, and IgG2b isotypes and were found to express complement-med iated bactericidal activity against N. meningitidis. These observations ind icate that recombinant B. pertussis may be a promising vector for the devel opment of a mucosal vaccine against serogroup B meningococci.