Genetic diversity and levels of expression of factor H binding protein among carriage isolates of Neisseria meningitidis

Abstract

The prevention of meningococcal disease may be improved by recombinant vaccines such as 4CMenB and rLP2086 that target the factor H binding protein (fHbp), an immunogenic surface component of Neisseria meningitidis present as one of three variants. Whether such vaccines decrease carriage of invasive isolates and thus induce herd immunity is unknown. We analyzed the genetic diversity and levels of expression of fHbp among 268 carriage strains and compare them to those of 467 invasive strains. fhbp gene sequencing showed higher proportions of variants 2 and 3 among carriage isolates (p<0.0001). Carriage isolates expressed lower levels of fHbp (p<0.01) but that remain high enough to predict targeting by antibodies against fHbp particularly in group B isolates belonging to the frequent hypervirulent clonal complexes in Europe and North America (cc32, cc41/44, cc269). This suggests that fHbp targeting meningococcal vaccines might reduce, at least in part, the acquisition of some hyperinvasive isolates.

Trial registration: ClinicalTrials.gov NCT01214850.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Phylogenetic relationships between carriage and invasive isolates.

On the right side of the figure the carriage isolates are displayed (n = 124). The invasive isolates for which full MLST data were available (n = 126) are on the left side of the figure. Relationships and clustering of typing data were performed using the START package available through (http://pubmlst.org).

Figure 2. Schematic representation of the levels of expression of fHbp overtime among carriage isolates.

Data were obtained from 80 subjects for whom two positive pharyngeal swabs were available at a mean of 1 weak interval. For each subject, the data were expressed as ratio of the expression of fHbp from the fist sample and the reference isolate and linked by a solid line to the ratio of the expression of fHbp from the second sample and the reference isolate.

Figure 3. Distribution of relative levels of expression of fHbp among carriage and invasive isolates.

Data were expressed as ratios of the expression for each strain compared to a reference strain a scatter plots (filled gray circles) and mean values (black lines). The clonal complexes (cc) to which belong the tested isolates are indicted under each group of scatter plots.