Kinetics of Meningococcal Serogroup C-Specific Functional Antibody Levels Up to 15 Years after a Single Immunization with a Meningococcal Serogroup C Conjugate Vaccine during Adolescence

Abstract

Adolescent vaccination is now considered the key factor for offering direct protection against meningococcal disease but also for reducing carriage and transmission and, in this way, establishing herd protection. This study estimated age-dependent patterns in functional meningococcal serogroup C (MenC) antibody kinetics after primary MenC conjugate (MenCC) vaccination in adolescents. Serum samples (n = 1,676) were drawn from 2006 to 2011 from individuals aged 9 to 18 years at the time of primary MenCC vaccination in 2002. Functional antibody levels were measured with a serum bactericidal antibody assay (SBA) using rabbit complement. SBA titers gradually declined with time. Up to 9 years after primary vaccination, SBA titers were estimated to be higher in individuals who were aged 13 to 18 years at priming than in those who were aged 9 to 10 years at priming. Based on a linear mixed model, the higher functional antibody levels with age seem to be due to the achievement of higher peak levels upon vaccination rather than to lower rates of decline. It is estimated that 35 to 50% of individuals who received a single primary MenCC vaccination at an age of 9 to 18 years in 2002 will still have sufficient protective antibody levels 15 years later. Using a linear mixed model based on cohort data for a single dated serum sample per person, we were able to estimate the level of protection against MenC up to 15 years after a single vaccination. The current study shows that analysis of antibody kinetics can be done using cross-sectional serology data and is therefore relevant for future serosurveillance studies.

Keywords: Neisseria meningitidis; adolescent; antibodies; long-term; meningococcal serogroup C conjugate vaccine.

FIG 1

Serum bactericidal antibody assay (SBA) geometric mean titers (GMTs) (A) and proportions (%) of individuals with SBA titers of ≥8 (B) throughout the years 2006 to 2011 for individuals who received a single primary meningococcal serogroup C conjugate (MenCC) vaccination in 2002, at an age of 9 to 18 years. Each year represents a separate cohort of individuals (i.e., the data are nonlongitudinal). Error bars indicate 95% confidence intervals. SBA GMTs and the proportions of individuals with SBA titers of ≥8 declined gradually with time.

FIG 2

Peak SBA titers and subsequent decay in age cohorts of individuals who received a single primary MenCC vaccination in 2002, at an age of 9 to 10 (blue lines), 13 to 14 (gray lines), or 17 to 18 (red lines) years. Each set of lines represents the model-estimated mean and its 95% CI for one of the three age categories of the study population. Individual symbols represent the measured titers.

FIG 3

Peak SBA titers (A) and decay rates of SBA titers (B) after the single primary MenCC vaccination in 2002 in individuals aged 9 to 18 years. Each set of lines represents the model-estimated population mean and 95% CI. The peak SBA titer upon vaccination increased with age and was highest in those primed at the age of 17 to 18 years. The rates of antibody decay appeared to be similar across ages.

FIG 4

Model-estimated proportions of protected individuals (SBA titers of ≥8) up to 15 years after a single primary MenCC vaccination in 2002, at an age of 9 to 18 years. It is estimated that 15 years after the primary MenCC vaccination, 35 to 50% of this population will have SBA titers of ≥8.