Adolescents who received a single dose of MenACWY-CRM had evidence of enduring immune responses a median of 22 months after a single dose of vaccine. The proportions of participants with hSBA titers ≥8 among MenACWY-CRM recipients were significantly higher than in the vaccine-naïve control group for all serogroups and for serogroups A, W-135 and Y compared with recipients of MCV4. A similar pattern of statistical differences between the two vaccines was seen 1 month post-vaccination.6
While higher GMTs immediately following vaccination are of uncertain clinical relevance generally, in this study, higher GMTs established initially corresponded with statistically higher proportions of subject exceeding the protective threshold of hSBA titers ≥8 nearly two years later. Overall, the percentage of subjects with hSBA titers ≥8 ranged from 54–84% for serogroups C, W and Y and 25–36% for serogroup A. Although the between-group statistical differences in persistence are clearly apparent, the interpretation of these results with respect to duration of disease protection is complicated. Additionally, while presence of bactericidal antibodies has been associated with protection against disease caused by serogroup C, and by inference other serogroups, the absence of bactericidal antibodies may not indicate susceptibility.5,8
Studies of complement sources for use in assays evaluating meningococcal vaccines have been of interest since the development of the serogroup C meningococcal conjugate vaccines.2,4,5,9–11
As expected based on existing knowledge about the differences in human and rabbit as sources of complement for bactericidal assays, the titers measured by rSBA greatly exceeded those generated by hSBA.12
Previous studies have found a lack of correlation between hSBA and rSBA results;12
however, our data did not detect any instances where the rSBA results contradicted the hSBA results. For serogroups A, W-135 and Y, MenACWY-CRM recipients were significantly more likely than MCV4 recipients to have evidence of bactericidal antibodies almost 2 years after vaccination, regardless of the complement source used, while the proportions of subjects achieving rSBA or hSBA titers ≥8 were similar for serogroup C in recipients of both vaccines. While serogroup C disease remains of particular epidemiologic concern globally, in several countries including the United States, serogroup Y has emerged as a significant contributor to invasive disease incidence.13
One limitation of this study is that the population represented only a subset of the full cohort of subjects vaccinated in the initial study.6
Nevertheless, the consistency of results among the cohorts included in the persistence study and those in the primary study indicate that the immune responses of the subset were representative of the full cohort, minimizing concerns about selection bias. Another limitation of the current report is that it did not identify the critical point at which protection was no longer evident. Predefined assessments in future years are intended to provide this information. In addition, it was observed that the naïve controls were, on average, slightly younger than the age matched subjects from the parent study. This can be explained by the fact that the controls were enrolled to match within a range of ages relative to the vaccinated subjects, but because of the routine utilization of MCV4 in adolescents as per ACIP guidelines,14
it was relatively more difficult to identify controls at the higher ends of the range than at the lower end. The consequence is that this could have the effect of slightly underestimating the background rate of naturally acquired immunity to meningococcal disease, though given the slow pace by which natural immunity is acquired over time,15
it seems unlikely that this would be a significant limitation.
In summary, recipients of the MenACWY-CRM was immunogenic at the post-primary (1 month) and demonstrated strong persistence at a median of 22 months post vaccination, and led to a statistically higher proportion of subjects with hSBA titers ≥8 for serogroups A, W-135 and Y than did MCV4. Given that hSBA titers have been correlated with protection against invasive meningococcal disease due to serogroup C,5,16
these results may infer a potential advantage of the MenACWY-CRM vaccine over time, and may be relevant in determining the need for, and/or timing of a booster dose of meningococcal vaccine for older adolescents.