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.
Highlights
Invasive meningococcal diseases (IMD) such as meningitis and meningococcemia remain in all countries one of the leading cause of death from bacterial infection in otherwise healthy young subjects [1]
We reported here the first study that had analyzed the levels of surface expression of factor H binding protein (fHbp) among N. meningitidis isolates from healthy carriers, and compared them to those observed among invasive isolates collected in the same period on a same country
This fHbp expression is expected to be critical for the bacterial coverage of the new recombinant meningococcal vaccines, which are supposed to act by decreasing the risk of IMD at the individual level among immunized subjects, and by avoiding the decreasing acquisition/transmission of virulent strains and to induce herd immunity [20]
Summary
Invasive meningococcal diseases (IMD) such as meningitis and meningococcemia remain in all countries one of the leading cause of death from bacterial infection in otherwise healthy young subjects [1]. Numerous studies have shown that disease isolates (i.e. isolates from IMD cases) differ from carriage isolates, belonging to a limited number of genetic lineages or clonal complexes (cc) known for their virulence [3]. Most IMD in Europe, America and Oceania are due to group B isolates [6] Their prevention might be revolutionized at short term by a recently licensed recombinant vaccine containing 4 components (4CMenB/Bexsero) that is expected to offer a broad group B isolates coverage [7]. Another bivalent recombinant vaccine (rLP2086) is under development [8]. Because fHbp exists in non group B meningococcal isolates, a coverage of some of these isolates is expected, as recently shown for 4CMenB/ Bexsero against some group X isolates (from Africa but not from Europe) [9]
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