title: Comparing pneumococcal conjugate vaccine schedules based on 3 and 2 primary doses: systematic review and meta-analysis.
abstract: BACKGROUND
  Pneumococcal conjugate vaccines (PCV) were first licensed for use with 3 primary doses in infancy and a booster dose. The evidence for the effects of different schedules was examined in this systematic review and meta-analysis.
  
  
  METHODS
  We searched 12 databases and trial registers up to March 2010. We selected randomised controlled trials (RCTs), cohort and case-control studies making direct comparisons between PCV schedules with (2p) or (3p) primary doses, with (+1) or without (+0) a booster dose. We extracted data on clinical, nasopharyngeal carriage and immunological outcomes and used meta-analysis to combine results where appropriate.
  
  
  RESULTS
  Seropositivity levels (antibody concentration ≥0.35 μg/ml) following 3p and 2p PCV schedules were high for most serotypes (5 RCTs). Differences between schedules were generally small and tended to favour 3p schedules, particularly for serotypes 6B and 23F; between-study heterogeneity was high. Seropositivity levels following 3p+1 and 2p+1 schedules were similar but small differences favouring 3p+1 schedules were seen for serotypes 6B and 23F. We did not identify any RCTs reporting clinical outcomes for these comparisons. In 2 RCTs there was weak evidence of a reduction in carriage of S. pneumoniae serotypes included in the vaccine when 3p+0 schedules were compared to 2p+0 at 6 months of age.
  
  
  CONCLUSIONS
  Most data about the relative effects of different PCV schedules relate to immunological outcomes. Both 3p and 2p schedules result in high levels of seropositivity. The clinical relevance of differences in immunological outcomes between schedules is not known. There is an absence of clinical outcome data from RCTs with direct comparisons of any 2p with any 3p PCV schedule.
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.
authors.forename: Pippa
authors.initials: P
authors.lastname: Scott
authors.forename: Anne W S
authors.initials: AW
authors.lastname: Rutjes
authors.forename: Lilian
authors.initials: L
authors.lastname: Bermetz
authors.forename: Nadège
authors.initials: N
authors.lastname: Robert
authors.forename: Susana
authors.initials: S
authors.lastname: Scott
authors.forename: Tania
authors.initials: T
authors.lastname: Lourenço
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Nicola
authors.initials: N
authors.lastname: Low
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D002353:Carrier State / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods*; D007223:Infant; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D015995:Prevalence; D014611:Vaccination / Q000379:methods*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate