Comparing pneumococcal conjugate vaccine schedules based on 3 and 2 primary doses: systematic review and meta-analysis

BACKGROUND: Pneumococcal conjugate vaccines (PCV) were first licensed for usewith 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. Weselected randomised controlled trials (RCTs), cohort and case-control studiesmaking 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 tocombine 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 betweenschedules were generally small and tended to favour 3p schedules, particularlyfor serotypes 6B and 23F; between-study heterogeneity was high. Seropositivitylevels following 3p+1 and 2p+1 schedules were similar but small differencesfavouring 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 wasweak evidence of a reduction in carriage of S. pneumoniae serotypes included inthe 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 schedulesrelate to immunological outcomes. Both 3p and 2p schedules result in high levels of seropositivity. The clinical relevance of differences in immunologicaloutcomes 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.