title: Vaccine-induced IgG antibodies to the linear epitope on the PorB outer membrane protein promote opsonophagocytosis of Neisseria meningitidis by human neutrophils.
abstract: The serotype 15 PorB protein of Neisseria meningitidis contains an N-terminal linear immunodominant B-cell epitope located on the putative loop 1 (VR1) region. This epitope has previously been shown to stimulate antibody formation in 74% of the vaccinees after three doses of the Norwegian group B outer-membrane vesicle (OMV) vaccine. In the present study, the purified PorB protein and the 23mer synthetic peptide D63b2 covering VR1 region were immobilized onto N-hydroxysuccinimide-activated matrix and used for affinity purification of the specific IgG antibodies from sera of three selected vaccinees. PorB- and peptide D63b2-specific IgG preparations bound to the PorB protein on immunoblots and reacted with strain 44/76 and OMV complexes expressing the serotype 15 PorB protein, but not with the PorB-deficient mutant, suggesting high specificity for the PorB protein. Both PorB- and peptide D63b2-specific IgG were marginally bactericidal, but enabled strong opsonophagocytosis measured as respiratory burst response of human neutrophils and internalization of opsonized FTTC-labeled meningococci. The data indicate that about 30-57% of the bulk serum opsonic activity for the 44/76 bacteria could be ascribed to linear epitope-specific IgG1, thus contributing to vaccine-induced protection against systemic meningococcal disease via the opsonophagocytic route of pathogen clearance.
authors.affiliation: Department of Vaccinology, National Institute of Public Health, Oslo, Norway. Alexei.Delvig@ncl.ac.uk
authors.forename: A A
authors.initials: AA
authors.lastname: Delvig
authors.forename: T E
authors.initials: TE
authors.lastname: Michaelsen
authors.forename: A
authors.initials: A
authors.lastname: Aase
authors.forename: E A
authors.initials: EA
authors.lastname: Hoiby
authors.forename: E
authors.initials: E
authors.lastname: Rosenqvist
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008297:Male; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins / Q000097:blood / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D018272:Porins; D011487:Protein Conformation
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D018272:Porins; C057699:porin protein, Neisseria