Meningococcal vaccination in adolescents and adults induces bactericidal activity against hyperinvasive complement-resistant meningococcal isolates

BackgroundComplement-mediated killing is critical in the defense against meningococci. During a recent outbreak of invasive meningococcal serogroup W disease (IMD-W) in the Netherlands, the predominant isolates belonged to clonal complex (cc) 11, which may suggest a role for cc11-assocated traits in complement resistance. We investigated complement resistance of invasive and carriage meningococcal isolates of different serogroups and lineages. In addition, we investigated whether vaccine-induced antibodies can overcome resistance to complement-mediated killing. MethodsWe analyzed IMD isolates (n=56) and carriage isolates (n=19) of different serogroups and clonal lineages in the serum bactericidal antibody (SBA) assay using pooled serum from unvaccinated and vaccinated individuals. Furthermore, we determined meningococcal serogroup W geometric mean titers (GMTs) and protection levels with the routinely-used non-cc11 isolate and hyperinvasive cc11 isolates using individual serum samples from adolescents and adults 5 years postvaccination. ResultsThe hyperinvasive IMD isolates showed high variation in their resistance to complement-mediated killing when pooled serum from unvaccinated individuals was used (median 96, range 2-1,536). When pooled sera from vaccinated individuals was used, all isolates were killed. The minimum spanning tree revealed moderate clustering of serogroup and cc, while complement resistance did not. While a significantly lower GMT was observed against cc11 meningococcal serogroup W (MenW) compared to a non-cc11 MenW isolate in vaccinated adults but not in adolescents, we found no differences in the proportion protected between these isolates. ConclusionsThese data show that vaccine-induced antibodies are effectively inducing complement-mediated killing of complement-resistant hyperinvasive and carriage meningococcal isolates. Short summaryMeningococcal isolates of hyperinvasive lineages are resistant to complement-mediated killing but vaccine-induced antibodies effectively kill these invasive isolates.