Seroprevalence of bactericidal and anti-outer membrane vesicle antibodies to Neisseria meningitidis group B in England.

Outer membrane vesicle (OMV) and recombinant protein-based vaccines targeted against multiple strains of group B meningococci are under development. The serum bactericidal antibody (SBA) assay has been designated the surrogate of protection, but the exact cutoff has not been determined. We measured the SBA titers in 2,415 serum samples and the anti-OMV IgG antibody concentrations in 2,672 serum samples representative of the English population to establish a baseline of natural immunity. SBA and anti-OMV IgG antibody titers are high in infants in the first 3 months of life, declining thereafter, presumably as maternal immunity wanes. About 6% of the subjects in the 1- to 11-year-old age group had SBA titers >or=4. During the teenage years, there was a marked increase in the percentage of subjects with SBA titers >or=4, rising to over 50% in 19-year-olds, with about 20% of older adults achieving this titer. The peak in SBA and anti-OMV IgG titers coincided with the peak in meningococcal carriage. Simple mathematical models confirm that the relationship between observed seroprevalence and carriage by age is consistent with carriage inducing SBA and that following an episode of carriage, SBA levels may remain elevated for many months. With the exception of children aged 3 to 11 months, there was no clear relationship between disease incidence and seroprevalence.

Comparison and correlation of neisseria meningitidis serogroup B immunologic assay results and human antibody responses following three doses of the Norwegian meningococcal outer membrane vesicle vaccine MenBvac.

The prediction of efficacy of Neisseria meningitidis serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease.