Vaccine-Induced IgG Antibodies to the Linear Epitope on the PorB Outer Membrane Protein Promote Opsonophagocytosis ofNeisseria meningitidisby Human Neutrophils

Abstract

The serotype 15 PorB protein ofNeisseria meningitidiscontains 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 ontoN-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 FITC-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.