title: Recombinant Neisseria meningitidis transferrin binding protein A protects against experimental meningococcal infection.
abstract: To better characterize the vaccine potential of Neisseria meningitidis transferrin binding proteins (Tbps), we have overexpressed TbpA and TbpB from Neisseria meningitidis isolate K454 in Escherichia coli. The ability to bind human transferrin was retained by both recombinant proteins, enabling purification by affinity chromotography. The recombinant Tbps were evaluated individually and in combination in a mouse intraperitoneal-infection model to determine their ability to protect against meningococcal infection and to induce cross-reactive and bactericidal antibodies. For the first time, TbpA was found to afford protection against meningococcal challenge when administered as the sole immunogen. In contrast to the protection conferred by TbpB, this protection extended to a serogroup C isolate and strain B16B6, a serogroup B isolate with a lower-molecular-weight TbpB than that from strain K454. However, serum from a TbpB-immunized rabbit was found to be significantly more bactericidal than that from a TbpA-immunized animal. Our evidence demonstrates that TbpA used as a vaccine antigen may provide protection against a wider range of meningococcal strains than does TbpB alone. This protection appears not to be due to complement-mediated lysis and indicates that serum bactericidal activity may not always be the most appropriate predictor of efficacy for protein-based meningococcal vaccines.
authors.affiliation: Centre for Applied Microbiology and Research, Salisbury SP4 0JG, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: West
authors.forename: K
authors.initials: K
authors.lastname: Reddin
authors.forename: M
authors.initials: M
authors.lastname: Matheson
authors.forename: R
authors.initials: R
authors.lastname: Heath
authors.forename: S
authors.initials: S
authors.lastname: Funnell
authors.forename: M
authors.initials: M
authors.lastname: Hudson
authors.forename: A
authors.initials: A
authors.lastname: Robinson
authors.forename: A
authors.initials: A
authors.lastname: Gorringe
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics / Q000627:therapeutic use*; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D033862:Iron-Binding Proteins; D008589:Meningococcal Infections / Q000401:mortality / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000627:therapeutic use*; D051379:Mice; D009345:Neisseria meningitidis; D010532:Peritoneal Diseases / Q000517:prevention & control; D033863:Transferrin-Binding Proteins; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000627:therapeutic use
chemical_list: D000907:Antibodies, Bacterial; D002352:Carrier Proteins; D033862:Iron-Binding Proteins; D022401:Meningococcal Vaccines; D033863:Transferrin-Binding Proteins; D014614:Vaccines, Synthetic