title: Immunogenicity of 13-valent pneumococcal conjugate vaccine administered according to 4 different primary immunization schedules in infants: a randomized clinical trial.
abstract: OBJECTIVE
  Immunization schedules with pneumococcal conjugate vaccine (PCV) differ among countries regarding the number of doses, age at vaccinations, and interval between doses.
  
  
  OBJECTIVE
  To assess the optimal primary vaccination schedule by comparing immunogenicity of 13-valent PCV (PCV13) in 4 different immunization schedules.
  
  
  METHODS
  An open-label, parallel-group, randomized clinical trial of healthy term infants in a general community in The Netherlands conducted between June 30, 2010, and January 25, 2011, with 99% follow-up until age 12 months.
  
  
  METHODS
  Infants (N = 400) were randomly assigned (1:1:1:1) to receive PCV13 either at ages 2, 4, and 6 months (2-4-6); at ages 3 and 5 months (3-5); at ages 2, 3, and 4 months (2-3-4); or at ages 2 and 4 months (2-4), with a booster dose at age 11.5 months.
  
  
  METHODS
  Primary outcome measure was antibody geometric mean concentrations (GMCs) against PCV13-included serotypes 1 month after the booster dose measured by multiplex immunoassay. Secondary outcomes included GMCs measured 1 month after the primary series, at 8 months of age, and before the booster.
  
  
  RESULTS
  The primary outcome, GMCs at 1 month after the booster dose, was not significantly different between schedules for 70 of 78 comparisons. The 2-4-6 schedule was superior to the 2-3-4 schedule for serotypes 18C (10.2 µg/mL [95% CI, 8.2-12.7] vs 6.5 µg/mL [95% CI, 5.4-7.8]) and 23F (10.9 µg/mL [95% CI, 9.0-13.3] vs 7.3 µg/mL [95% CI, 5.8-9.2]) and superior to the 2-4 schedule for serotypes 6B (8.5 µg/mL [95% CI, 7.1-10.2] vs 5.1 µg/mL [95% CI 3.8-6.7]), 18C (6.6 µg/mL [95% CI, 5.7-7.7]), and 23F (7.2 µg/mL [95% CI, 5.9-8.8]). For serotype 1, the 3-5 schedule (11.7 µg/mL [95% CI, 9.6-14.3]) was superior to the other schedules. Geometric mean concentrations for all 13 serotypes ranged between 1.6 and 19.9 µg/mL. Secondary outcomes demonstrated differences 1 month after the primary series. The 2-4-6 schedule was superior compared with the 3-5, 2-3-4, and 2-4 schedules for 3, 9, and 11 serotypes, respectively. Differences between schedules persisted until the booster dose.
  
  
  CONCLUSIONS
  The use of 4 different PCV13 immunization schedules in healthy term infants resulted in no statistically significant differences in antibody levels after the booster dose for almost all serotypes. The choice of PCV schedule will require a balance between the need for early protection and maintaining protection between the primary series and the booster.
  
  
  BACKGROUND
  trialregister.nl Identifier: NTR2316.
authors.affiliation: Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands. j.spijkerman@umcutrecht.nl
authors.forename: Judith
authors.initials: J
authors.lastname: Spijkerman
authors.forename: Reinier H
authors.initials: RH
authors.lastname: Veenhoven
authors.forename: Alienke J
authors.initials: AJ
authors.lastname: Wijmenga-Monsuur
authors.forename: Karin E M
authors.initials: KE
authors.lastname: Elberse
authors.forename: Pieter G M
authors.initials: PG
authors.lastname: van Gageldonk
authors.forename: Mirjam J
authors.initials: MJ
authors.lastname: Knol
authors.forename: Hester E
authors.initials: HE
authors.lastname: de Melker
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.forename: Leo M
authors.initials: LM
authors.lastname: Schouls
authors.forename: Guy A M
authors.initials: GA
authors.lastname: Berbers
mesh_terms: D000917:Antibody Formation / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D009426:Netherlands; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: C538862:13-valent pneumococcal vaccine; D022242:Pneumococcal Vaccines