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

Grants and funding

This study was funded by the Dutch Ministry of Health. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Baxter kindly provided the vaccines.