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

PLoS One. 2014 Jun 25;9(6):e100651. doi: 10.1371/journal.pone.0100651. eCollection 2014.

Abstract

Background: Meningococcal 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.

Methods: A 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.

Results: 258 (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.

Conclusion: Nine 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 registration: EU Clinical Trials Database 2011-000375-13 Dutch Trial Register NTR3521.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Bacterial / immunology
  • Antibody Specificity
  • Child
  • Female
  • Humans
  • Immunization, Secondary / methods*
  • Immunoglobulin G / immunology
  • Male
  • Meningococcal Vaccines / immunology*
  • Netherlands
  • Tetanus Toxoid / immunology
  • Time Factors
  • Vaccination
  • Vaccines, Conjugate / immunology

Substances

  • Antibodies, Bacterial
  • Immunoglobulin G
  • Meningococcal Vaccines
  • Tetanus Toxoid
  • Vaccines, Conjugate
  • serogroup C meningococcal conjugate vaccine

Associated data

  • NTR/NTR3521