Age-related immunity to meningococcal serogroup C vaccination: an increase in the persistence of IgG2 correlates with a decrease in the avidity of IgG

Abstract

Background: All children and adolescents between 1 and 19 years of age in The Netherlands received a single meningococcal serogroup C conjugate (MenCC) vaccine in 2002. During follow-up 4-5 years later, the persistence of MenC polysaccharide-specific IgG was found to be dependent on age of vaccination with higher IgG levels in the oldest immunized age categories.

Methods and findings: Two cross-sectional population-based serum banks, collected in 1995/1996 and in 2006/2007, were used for this study. We measured MenC polysaccharide-specific IgM, the IgG1 and IgG2 subclasses and determined the avidity of the IgG antibodies. We report that the age-related persistence of IgG after immunization with the MenCC vaccine seemed to result from an increase of IgG2 levels with age, while IgG1 levels remained stable throughout the different age-cohorts. Furthermore, an age-related increase in IgM levels was observed, correlating with the persistence of IgG antibodies with age. It is noteworthy that the increase in IgG2 correlated with a reduced IgG-avidity with age.

Conclusion: These date indicate that the classical characteristics of a T-cell-dependent antibody response as elicited by protein based vaccines might not be completely applicable when conjugate vaccines are administered to older children and adolescents up to 18 years of age. The response elicited by the MenCC vaccine seemed to be more a mixture of both T cell dependent and T cell independent responses in terms of humoral immunological characteristics.

Figure 1. Meningococcal serogroup C PS-specific IgM levels.

Levels of IgM in the pre-MenC introduction era are shown in grey bars, the post-MenC introduction era are shown in black bars. Routine immunization is offered in the post-MenC introduction era at 14 months of age and children and adolescents between 5–21 years of age received a single immunization 4–5 years earlier. Error bars indicate 95% confidence intervals. Age at bloodsampling is indicated in years or as stated otherwise (mo  =  age in months).

Figure 2. Meningococcal serogroup A and C PS-specific IgG1/IgG2 ratios (grey and black bars, respectively).

An IgG1/IgG2 ratio of >1 indicates a higher level of IgG1; an IgG1/IgG2 ratio of <1 indicates a higher level of IgG2. MenCC immunization is offered at 14 months of age and children and adolescents between 5–21 years of age received a single immunization 4–5 years earlier. Error bars indicate 95% confidence intervals. Age at bloodsampling is indicated in years or as stated otherwise (mo  =  age in months).

Figure 3. Avidity of Meningococcal serogroup C PS-specific IgG.

Sera with an avidity indices (AI) of 0–33 are indicated as low AI (in black), sera with an AI of 34–66 are determined to be of intermediate AI (in white) and sera with an AI of 67–100 are assigned to be of high AI (in grey). Age at bloodsampling is indicated in years or as stated otherwise (mo  =  age in months).

Figure 4. Correlation between levels of Meningococcal serogroup C PS-specific IgG, IgG1, IgG2 and IgG avidity within immunized or non-immunized cohorts in the post-immunization era.

A) Concentrations of IgG, IgG1, IgG2 and the percentage of persons with a relatively low AI in each cohort. B) Correlation between IgG1 and IgG in the 11 immunized cohorts (15 months to 21 years of age, filled triangles) or in the 4 non-immunized cohorts (22 to 79 years of age, open triangles). C) Correlation between IgG2 and IgG in the 11 immunized cohorts (15 months to 21 years of age, filled circles) or in the 4 non-immunized cohorts (22 to 79 years of age, open circles). D) Correlation between IgG1 and the percentage of individuals with low AI in the 11 immunized cohorts (15 months to 21 years of age, filled triangles) or in the 4 non-immunized cohorts (22 to 79 years of age, open triangles). E) Correlation between IgG2 and the percentage of individuals with low AI in the 11 immunized cohorts (15 months to 21 years of age, filled triangles) or in the 4 non-immunized cohorts (22 to 79 years of age, open triangles). F) Comparison of the AI's of sera with an IgG1/IgG2 ratio >1 and an IgG1/IgG2 ratio <1. * P<0.0001.