title: Timing of an adolescent booster after single primary meningococcal serogroup C conjugate immunization at young age; an intervention study among Dutch teenagers.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  EU Clinical Trials Database 2011-000375-13 Dutch Trial Register NTR3521.
authors: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors: Susanne P
authors: SP
authors: Stoof
authors: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors: Fiona R M
authors: FR
authors: van der Klis
authors: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors: Debbie M
authors: DM
authors: van Rooijen
authors: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors: Mirjam J
authors: MJ
authors: Knol
authors: Department of Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
authors: Elisabeth A M
authors: EA
authors: Sanders
authors: Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors: Guy A M
authors: GA
authors: Berbers
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000276:immunology; D000918:Antibody Specificity; D002648:Child; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D022401:Meningococcal Vaccines / Q000276:immunology*; D009426:Netherlands; D013745:Tetanus Toxoid / Q000276:immunology; D013997:Time Factors; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C410218:serogroup C meningococcal conjugate vaccine