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

Abstract

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.

FIG. 1.

Percentage of sera with SBA titers ≥2, ≥4, and ≥8, by age.

FIG. 2.

Age-specific IgG OMV ELISA GMTs and 95% confidence intervals.

FIG. 3.

Age-specific incidence of serogroup B disease compared to the percentage of individuals with SBA titers ≥4.

FIG. 4.

Model fit to group B SBA and carriage data. This model assumes that the average duration of group B carriage is 6 months. Other parameters were estimated (Table 1). *, categories M (maternal immunity) and I (acquired immunity) are combined.

FIG. 5.

Age-specific seroprevalence of SBA antibodies to group B and group C reference strains in the United Kingdom.