This study has demonstrated a difference in the immune responses to serogroups A and C after repeated vaccination with the meningococcal polysaccharide vaccine in Saudi residents aged 10 to 29 years.
This is the first published report of a study measuring the functional antibody response to demonstrate an increase in the titer of SBA to the serogroup A polysaccharide following repeated polysaccharide vaccination in individuals in this age group. Postvaccination, the serogroup A GM SBA titer in subjects who had previously received two or more doses of polysaccharide vaccine was higher than the titer in those receiving it for the first time (P = 0.042). The number of responders (SBA titer, ≥8) increased from 69% in the naïve group to 100% in the postvaccination group after at least two doses. Serogroup A-specific GM IgG concentrations also increased following vaccination. The highest IgG concentration 1 month after vaccination was detected among those who had been vaccinated two or more times.
The results of this study support those of other studies (15
) that have indicated that repeated doses of serogroup A meningococcal polysaccharide vaccine induce sustained levels of antibody to the serogroup A polysaccharide. However, the three previous studies (15
) showed an induction of the immune response to serogroup A only by ELISA. Conversely, two studies (10
) demonstrated immunologic hyporesponsiveness to repeated vaccination with the serogroup A meningococcal polysaccharide vaccine. Those two studies measured both IgG concentrations (by ELISA) and SBA titers (10
Despite the use of bactericidal antibody assays together with the IgG concentration measurements, the conflicting results between this study and the two previous studies (10
) are obvious. The variation in results could be related to a number of different factors. First, the population sample size used in this study is much larger than those used in the previous two studies. Second, the populations used in the previous two studies were from different countries: Gambia (29
) and the United Kingdom (10
). Also, the Gambian study (29
) recruited children aged 5 years during a vaccination campaign after an outbreak of serogroup A meningococcal disease. Those children had previously received two doses of the vaccine at the ages of 3 to 6 months and 18 to 24 months, respectively. The study conducted in the United Kingdom (10
) recruited university students aged 18 to 25 years who had been vaccinated only once 6 months earlier as part of preventive measures taken after an outbreak. It is clear that the populations selected in this study were different in several aspects, such as the ages compared to the ages of the subjects evaluated in the Gambian study (children) and the time since the last vaccination compared to that in the study conducted in the United Kingdom. Third, the vaccine given in the United Kingdom and Gambia (Pasteur Merieux) was produced by a company different from that which produced the vaccine used in the present study (GlaxoSmithKline). Finally, and most importantly, in this study the subjects were local residents of Makkah and Jeddah, where the rate of natural exposure could have been similar to that for Gambian children but completely different from that for the subjects evaluated in the United Kingdom, where serogroup A is very rarely reported. Furthermore, the subjects in the present study were potentially exposed to serogroup A and W135 meningococci during the Hajj 2000 outbreak, when both serogroups were isolated from case patients (28
Avidity indices have previously been used to investigate the maturation of long-lived B cells following vaccination with meningococcal serogroup A and C polysaccharide and conjugate vaccines (9
). Antibody avidity, the strength with which a multivalent antibody binds to a complex antigen, increases over time following primary immunization with a T-cell-dependent antigen but decreases following immunization with T-cell-independent antigens. Joseph et al. (25
) demonstrated that following serogroup A polysaccharide immunization the avidity indices remained significantly above the prevaccination levels 1 year following vaccination among children 2 to 3 years of age, whereas after serogroup C polysaccharide vaccination, the avidity indices declined significantly postvaccination among children (9
). These findings also indicate that the serogroup A polysaccharide may not be behaving as a classical T-cell-independent antigen.
The proportions of putative responders postvaccination with the serogroup C polysaccharide were 81% for the naïve group and 48% for those who had received one prior polysaccharide vaccine. As shown in previously published studies, repeated doses of polysaccharide vaccine resulted in immune hyporesponsiveness (19
Repeated vaccination with the serogroup A and C polysaccharide vaccine gives reduced functional antibody responses to the serogroup C portion of the vaccine but increased responses to the serogroup A portion of the vaccine among residents of the cities of Makkah and Jeddah in Saudi Arabia aged 10 to 29 years. The reasons for this difference in response are unclear, but other bacterial polysaccharides have been reported to act in a T-cell-dependent fashion (34
Use of the conjugate vaccine should be considered for long-term protection against serogroup C disease. However, other serogroups (A, Y, and W135) will continue to cause problems, and trials with the quadrivalent meningococcal conjugate vaccine have commenced (11
). Once it is licensed, use of the quadrivalent meningococcal conjugate vaccine in Saudi Arabia will provide long-term protection and will be more cost-effective.