To our knowledge, this is the first report on the immune response to a quadrivalent A, C, Y, and W-135 conjugate vaccination in adolescents who had previously been vaccinated with bivalent A/C polysaccharide vaccine and an MPSV4 vaccine. This study has demonstrated that MCV4 induced robust immune responses in those who had received prior meningococcal polysaccharide vaccines and yielded no unusual safety signals.
Prior to vaccination, serogroup A rSBA GMTs in all 3 study groups were high compared to those of the other serogroups, which could be due to natural priming from the prior circulation of serogroup A meningococci in KSA. Similarly to serogroup A, there were no differences in the serogroup C rSBA GMTs of the three groups prevaccination. Higher serogroup C rSBA titers may have been expected in the PSV-exposed groups, but serogroup C rSBA titers have been shown to decline rapidly following polysaccharide vaccination (4
). For serogroups W-135 and Y, the prevaccination rSBA GMTs were lower in the PSV-naïve group, as expected.
Repeat doses of meningococcal polysaccharide vaccine can induce hyporesponsiveness, whereby persons previously vaccinated with meningococcal polysaccharide vaccine mount an immune response to revaccination with polysaccharide or conjugate vaccine that is lower in magnitude than the immune response of persons of a similar age being immunized for the first time (2
). Although the clinical significance of such hyporesponsiveness is not known, most experts would prefer to avoid it if is possible to do so with relative ease. Hyporesponsiveness was evident in this study for all four serogroups, as the rSBA GMTs after MCV4 vaccination in those who had received prior meningococcal polysaccharide vaccination were significantly lower than those of the PSV-naïve group. These results are consistent with previously reported data for serogroup C (8
). Further, Keyserling et al. (8
) reported lower SBA GMTs after MCV4 in U.S. adolescents who had received MPSV4 vaccination 3 years earlier, which is in agreement with the observations in this study.
This study demonstrated reduced rSBA responses to serogroup A after MCV4 administration in PS-exposed participants. Previous reports examining the response of multiple doses of serogroup A polysaccharide vaccine are conflicting. Several studies have demonstrated a boosting effect to repeated doses of serogroup A polysaccharide vaccine (4
), whereas reduced responses have also been reported for this serogroup as well (2
). Lakshman et al. (10
) assessed immune responses to bivalent A/C polysaccharide or conjugate vaccine in young adults, and serogroup A hyporesponsiveness was seen after two doses of polysaccharide vaccine, but rSBA response to conjugate vaccine after a prior polysaccharide vaccine was not reduced compared to responses in naïve participants. The converse was seen in this study. A key difference between our study and that by Lakshman et al. (10
) is the mean time between MPSV4 vaccination, 38 months as opposed to 52 to 60 weeks, respectively.
In the PSV-exposed participants after either MCV4 or MPSV4 vaccination, no statistically significant differences in the postvaccination rSBA GMTs were observed for any of the 4 serogroups. However, there were consistently higher rSBA GMTs in those vaccinated with MCV4. The serogroup C rSBA response after MCV4 vaccination compared to that after MPSV4 vaccination in the PSV-exposed participants, without adjusting for prevaccination titers, were not significantly different. After the adjustment of the day 28 GMTs for the baseline titers using ANOVA, the serogroup C rSBA GMT was significantly higher after MCV4 than after MPSV4 vaccination.
The nature of local and systemic reactions did not materially differ between the study vaccines or for the administration of MCV4 as a booster or primary dose; the majority of solicited reactions were mild.
In conclusion, the findings from this study suggest that immunological hyporesponsiveness can happen with repeated doses of meningococcal polysaccharide vaccine for all 4 serogroups (A, C, Y, and W-135), and that quadrivalent meningococcal conjugate vaccination in those with a history of repeated polysaccharide vaccine receipt is safe and induces robust immune responses that may partially compensate for hyporesponsiveness.