Timing of an adolescent booster after single primary meningococcal serogroup C conjugate immunization at young age; an intervention study among Dutch teenagers.

Susanne P Stoof,Elisabeth A M Sanders,Fiona R M Van Der Klis,Mirjam J Knol,Debbie M Van Rooijen,Guy A M Berbers,Diane Medved Harper

doi:10.1371/journal.pone.0100651

Abstract

BackgroundMeningococcal serogroup C (MenC) specific antibody levels decline rapidly after a single primary MenC conjugate (MenCC) vaccination in preschool children. A second MenCC vaccination during (pre)adolescence might attain longer lasting individual and herd protection. We aimed to establish an appropriate age for a (pre)adolescent MenCC booster vaccination.MethodsA phase-IV trial with healthy 10-year-olds (n = 91), 12-year-olds (n = 91) and 15-year-olds (n = 86) who were primed with a MenCC vaccine nine years earlier. All participants received a booster vaccination with the same vaccine. Serum bactericidal antibody assay titers (SBA, using baby rabbit complement), MenC-polysaccharide (MenC-PS) specific IgG, IgG subclass and avidity and tetanus-specific IgG levels were measured prior to (T0) and 1 month (T1) and 1 year (T2) after the booster. An SBA titer ≥8 was the correlate of protection.Results258 (96.3%) participants completed all three study visits. At T0, 19% of the 10-year-olds still had an SBA titer ≥8, compared to 34% of the 12-year-olds (P = 0.057) and 45% of the 15-year-olds (P<0.001). All participants developed high SBA titers (GMTs>30,000 in all age groups) and MenC-PS specific IgG levels at T1. IgG levels mainly consisted of IgG1, but the contribution of IgG2 increased with age. At T2, 100% of participants still had an SBA titer ≥8, but the 15-year-olds showed the highest protective antibody levels and the lowest decay.ConclusionNine years after primary MenCC vaccination adolescents develop high protective antibody levels in response to a booster and are still sufficiently protected one year later. Our results suggest that persistence of individual - and herd - protection increases with the age at which an adolescent booster is administered.Trial RegistrationEU Clinical Trials Database 2011-000375-13 Dutch Trial Register NTR3521

Highlights

Invasive meningococcal disease (IMD) is a severe illness, with a mortality rate of,10% and serious sequelae in a substantial number of survivors
A single Meningococcal Serogroup C conjugated (MenCC) vaccination was implemented into the Dutch National Immunization Programme (NIP) in 2002 for all children aged 14 months
Blood samples of the 1 month (T1) and 1 year (T2) follow-up were collected in November 2011 and October 2012, respectively. 258 participants (96.3%) completed all three study visits (Figure 1)

Summary

Introduction

Invasive meningococcal disease (IMD) is a severe illness, with a mortality rate of ,10% and serious sequelae in a substantial number of survivors. A single Meningococcal Serogroup C conjugated (MenCC) vaccination was implemented into the Dutch National Immunization Programme (NIP) in 2002 for all children aged 14 months. Far only three cases of vaccine failure have occurred, of which two had an underlying immune deficiency, and only a few cases of MenC disease occur yearly among unvaccinated individuals [4]. This successful elimination is likely due to the large-scale catch-up campaign that included adolescents [5,6]. Meningococcal serogroup C (MenC) specific antibody levels decline rapidly after a single primary MenC conjugate (MenCC) vaccination in preschool children. We aimed to establish an appropriate age for a (pre)adolescent MenCC booster vaccination

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