Vaccine-induced IgG antibodies to the linear epitope on the PorB outer membrane protein promote opsonophagocytosis of Neisseria meningitidis by human neutrophils.
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.
Delvig
A A
AA
Department of Vaccinology, National Institute of Public Health, Oslo, Norway. Alexei.Delvig@ncl.ac.uk
Michaelsen
T E
TE
Aase
A
A
Hoiby
E A
EA
Rosenqvist
E
E
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
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