Impact of CRM197-based conjugate vaccines, schedules, and regions on pneumococcal immunogenicity in young children: systematic review

Population-level introduction of pneumococcal conjugate vaccines (PCVs) has increased non-vaccine serotype invasive pneumococcal disease (IPD) incidence in children. Higher-valency PCVs were developed to address shifting disease-causing serotypes. This systematic review and meta-analysis defines trends in CRM197-based PCV immunogenicity in children < 2 years. We searched five databases-EMBASE, MEDLINE, Web of Science Core Collection, Global Health, and Cochrane Central Register of Controlled Trials. Random-effects meta-analyses were conducted using log-transformed IgG GMCs and logit-transformed seroresponse rates to generate pooled estimates. We included 250 articles from 138 study groups involving 243 study arms. Vaccine immunogenicity varied by serotype, vaccine, schedule and region. Pooled IgG GMCs post-childhood-schedule were lowest for serotype 3-PCV20 (0.84 μg/mL; 95%CI: 0.60-1.17), and highest for 15B-PCV20 (16.00 μg/mL; 95%CI: 12.31-20.80). Post-childhood-schedule seroresponse rates were >95% for all serotypes except 3. IgG responses increased with primary-dose number, and were further enhanced by a booster, although magnitude varied by serotype and vaccine; for PCV20, IgG GMCs after two-primary doses were still below the 0.35 µg/mL threshold for six serotypes. A general downward trend in IgG GMCs was observed with increasing vaccine valency. Regional variation in post-childhood-schedule IgG GMCs was observed, with highest GMCs in the Western Pacific Region.