Immunogenicity and seroefficacy of pneumococcal conjugate vaccines – a systematic review and network meta-analysis

Abstract

Background Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organisation. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Methods In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to July 2022 (Protocol PROSPERO ID CRD42019124580). Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials for young children, and provided at least one time point after the primary vaccination series and/or one-month after a booster dose. Individual participant level data were requested from publication authors and/or the relevant vaccine manufacturer; aggregate data were extracted if individual data were unavailable. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and relative risk (RR) of seroinfection. Seroinfection is defined as a rise in antibody between the primary vaccination series and the booster dose, as evidence of subclinical infection. We also estimated the relationship between the GMR one month after priming and the RR of seroinfection by the time of the booster dose. Findings In total 45 studies were eligible from 38 countries across six continents. 27 and 12 studies with data available were included in immunogenicity and seroefficacy analyses respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Two-fold higher antibody after primary vaccination was associated with 54% decrease in risk of seroinfection (RR 0.46, 95%CI 0.23-0.96). Conclusion Serotype-specific differences were found in immunogenicity and seroefficacy between PCV10 and PCV13. Higher immunogenicity of PCVs are associated with lower risk of subsequent infection. These findings could be further used to compare PCVs and optimise vaccination strategy.