The effect of 2 doses of polysaccharide vaccine on the response to a subsequent dose of conjugate vaccine in young children for serogroups A, C, Y, and W-135 had been unexamined to date. This study demonstrated that MCV4 was safe and induced protective immune responses in children who have previously received 2 doses of MPSV4. After MCV4 vaccination, the rSBA GMT responses appeared to be higher for all serogroups, especially for serogroup C, in those who were meningococcal polysaccharide vaccine naïve compared to those who had received MPSV4. In previous studies, repeated doses of serogroup C polysaccharide vaccine have been clearly documented to lead to immune hyporesponsiveness, while booster antibody responses have been observed for serogroup A with repeat dosing, underscoring the differences in these polysaccharide antigens (8
The effects of previous serogroup C polysaccharide vaccinations on responses to conjugate vaccination were studied in children in the United Kingdom (6
). In this study, 54 children (median age, 34 months; range, 4 to 62 months) previously vaccinated with a single dose of bivalent serogroup A and C meningococcal polysaccharide vaccine (MPV) were revaccinated 7 months later with monovalent serogroup C meningococcal conjugate vaccine (MCV). Their responses were compared to those from 122 MPV-naïve children who received only serogroup C MCV. For children vaccinated with MPV at <1 year of age (median age was estimated to be 8 months with a range of 5 to 11 months), the proportion of children with serogroup C rSBA titers of ≥8 as well as the rSBA GMTs were significantly lower than those for MPV-naïve children. For children vaccinated with MPV between 1 and 5 years of age, rSBA GMTs and the proportion of children protected after MCV administration were similar to those in the MPV-naïve children. Thus, the magnitude of the depressing effect by prior MPV on serogroup C responses to MCV is age dependent, with the greatest effect observed when MPV was administered to infants and young children. The difference between the serogroup C response to conjugate vaccination after prior polysaccharide treatment in the study reported here and the study conducted by Borrow et al. (6
) is the time between polysaccharide administration and conjugate vaccination, with a time gap of several years in this study compared to 7 months in the previous study (6
). The number of prior doses of MPV has also been demonstrated to affect the serogroup C response to subsequent monovalent serogroup C conjugate (MCC) vaccine. Serogroup C SBA GMTs were shown to be reduced following MCC vaccine in children who had received three prior doses of MPV compared to those who had only received one prior dose of MPV (16
In the present study, the serogroup C-specific IgG GMCs between the 2 groups did not differ; this reflects the differences between the IgG enzyme-linked immunosorbent assay (ELISA) and the SBA assay. The SBA assay, considered the gold standard for the quantitation of meningococcal antibody responses (5
), measures functional antibody against the whole meningococcus strain. Thus, the assay more completely assesses vaccine response and protection, as it detects vaccine-elicited antibodies regardless of isotype. This is opposed to serogroup-specific IgG concentration measurements that only assess capsular polysaccharide-specific IgGs with variable avidity to the ELISA-bound antigen (7
). Likewise, although the serogroup A SBA GMTs did not appear much different postvaccination between the two groups, the serogroup A-specific IgG GMCs were higher for those who had received prior MPSV4, again reflecting the differences in the two immunoassays. These discordant results between the two assays for serogroup A suggest that prior vaccination had an adverse effect on anticapsular antibody functional activity; that is, on average, twice the concentration of anticapsular serogroup A antibody was needed for complement-mediated lysis in those previously vaccinated than in naïve subjects. For serogroup C, the results suggest that the quality and not the quantity of the response was affected by prior vaccination because the IgG GMCs were similar, but significantly higher SBA GMTs were observed in the naïve group. These differences in serogroup A and C responses in the previously vaccinated group may reflect the differences in these polysaccharide antigens.
Discordant results between serogroup A SBA assay and ELISA results were demonstrated in a study of west African children aged 12 to 23 months who received either a single dose of quadrivalent A, C, Y, and W-135 polysaccharide vaccine or Haemophilus influenzae
type b (Hib) conjugate vaccine followed 10 months later by monovalent A conjugate vaccine (21
). The serogroup A SBA GMTs 28 days after conjugate vaccine were similar between those who received prior polysaccharide vaccine and those who did not, 6,708.9 (95% CI, 5097.6 to 8,829.5) and 9,342.9 (95% CI, 7,043.8 to 12,392.4), respectively, but the serogroup A-specific IgG GMCs were higher in those who had received prior polysaccharide treatment (38.1 μg/ml [95% CI, 29.7 to 48.9]) than in those who received the control Hib conjugate vaccine (15.4 μg/ml [95% CI, 11.7 to 20.2]).
The MCV4 safety profiles for the prior-MPSV4 group and the meningococcal vaccine-naive group were similar; a substantial majority of solicited adverse reactions were grade 1 in intensity, while grade 3 reactions were reported only for fever. This is similar to results reported after a single dose of MPSV4 in 2- to 10-year-old children from the United States (20
), and the results suggest that the safety of a single dose of the conjugated vaccines is similar to that of the polysaccharide vaccine.
In conclusion, this study has demonstrated that MCV4 vaccine elicited a robust immune response in children who previously received MPSV4. These data support the notion that children in the KSA who have previously received MPSV4 can be vaccinated with MCV4 without further aggravating previously induced hyporesponsiveness. Whether the response in both groups could be equally improved by a further booster of MCV4 would be of interest to our understanding of polysaccharide-induced hyporesponsiveness.