Development of immunity to serogroup B meningococci during carriage of Neisseria meningitidis in a cohort of university students

Abstract

Understanding the basis of protective immunity is a key requirement for the development of an effective vaccine against infection with Neisseria meningitidis of serogroup B. We have conducted a longitudinal study into the dynamics of meningococcal acquisition and carriage in first-year university students. The detection of carriage of serogroup B meningococci correlated with an increase in detection of serum bactericidal activity (SBA) against both colonizing and heterologous serogroup B strains. Once induced, SBA remained high throughout the study. Although students showed increases in antibodies reactive with capsular polysaccharide and lipopolysaccharide (LPS), these antibody responses were transitory, and their decline was not accompanied by a corresponding decline in SBA. In contrast, there was a significant correlation between the presence of antibodies to the PorA outer membrane protein and SBA against both homologous and heterologous strains. SBA induced by a PorA-negative mutant confirmed the contribution of PorA to heterologous activity. Increases in SBA against a range of serogroup B strains were also observed in students in whom no meningococcal carriage was detected. This heterologous protection could not be associated with the presence of antibodies reacting with capsule, LPS, PorA, PorB, Rmp, Opa, Opc, or pilin, demonstrating that other, as yet unidentified, antigens contribute to the development of immunity to serogroup B meningococci. Identification of such antigens with the ability to induce an effective cross-reactive bactericidal response to a range of strains would be a major step in the production of a universally effective vaccine against infections caused by serogroup B meningococci.

FIG. 1.

SBA of students against each serogroup B meningococcal carriage strain. Shown are the SBA titers of students (as numbered on the x axis of panel E) against each serogroup B strain detected in this study. Filled bars indicate the SBA titer at the start of the study (week 0), and open bars show bactericidal antibody levels at the end (week 31) of the study. Noncarriers and carriers are grouped by parentheses (as shown in panel E) on the x axis. Striped bars indicate bactericidal activity of carriers at week 31 against their homologous colonizing strain(s).

FIG. 2.

SBA of serogroup B carriers against all serogroup B meningococcal carriage strains. The SBA titers of individual students colonized by serogroup B meningococci are shown. The MC numbers (MC168 to MC172) are the designations of the serogroup B carriage strains detected in the present survey (Table 2). The arrows indicate the time point(s) at which serogroup B colonization was first detected. The four time points are shown in chronological order as indicated on the figure. Student 9 did not attend the second session; therefore, there is no data for this individual at that time point.

FIG. 3.

Serum antibodies directed against specific meningococcal components in serogroup B carriers. Antibodies directed against the serogroup B capsular polysaccharide (B cap) and LPS immunotypes L1 and L3 were determined by ELISA, and results are shown for individual students. The data are presented as antibody concentration levels obtained at each sampling time point as detailed in the legend of Fig. 2, with arrows indicating the time point(s) at which serogroup B colonization was first detected.

FIG. 4.

Antibody directed against meningococcal components in relation to SBA. Serum samples of carriers and noncarriers were reacted in ELISAs with serogroup B capsular polysaccharide (A), LPS immunotype L3 (B), and LPS immunotype L1 (C). Antibody levels are shown in relation to SBA against the serogroup B carriage strain MC171 at the same time point (week 31), and the bar indicates the geometric mean of the data collected. Similar results were obtained for the other strains. The immune data of serogroup B carriers are indicated by filled circles.