title: Vaccine potential of the Neisseria meningitidis lactoferrin-binding proteins LbpA and LbpB.
abstract: The vaccine potential of the Neisseria meningitidis lactoferrin-binding proteins LbpA and LbpB was evaluated. Sequencing and sequence alignments suggested that LbpA is relatively well conserved with variability largely restricted to two surface-exposed loops in a proposed topology model. Consistently, antisera raised against synthetic peptides corresponding to exposed loops generally recognized the LbpA proteins of many different strains. Hence, LbpA was considered an attractive vaccine candidate. LbpB shows a higher degree of sequence variability. For immunisation studies, LbpA was overproduced in N. meningitidis and a histidine-tagged LbpB protein was produced in Escherichia coli. Outer membrane vesicles carrying overproduced LbpA and purified LbpB were used to immunise laboratory animals. The bactericidal activity and cross-reactivity of the antibodies was evaluated using meningococcal strains of various clonal lineages. In addition, LbpB-specific monoclonal antibodies were analysed by Western blots and whole-cell enzyme-linked immunosorbent assays. Our results show that both proteins are immunogenic and able to induce bactericidal antibodies, but that the cross-reactivity of these antibodies is limited.
authors.affiliation: Department of Molecular Microbiology, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Annika
authors.initials: A
authors.lastname: Pettersson
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kortekaas
authors.forename: Vincent E
authors.initials: VE
authors.lastname: Weynants
authors.forename: Pierre
authors.initials: P
authors.lastname: Voet
authors.forename: Jan T
authors.initials: JT
authors.lastname: Poolman
authors.forename: Martine P
authors.initials: MP
authors.lastname: Bos
authors.forename: Jan
authors.initials: J
authors.lastname: Tommassen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001770:Blood Bactericidal Activity; D003429:Cross Reactions; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D016415:Sequence Alignment; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D007106:Immune Sera; C112566:LBPA protein, Neisseria meningitidis; D022401:Meningococcal Vaccines; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic