Comparative immunogenicity and safety of PCV15 versus PCV13 for pneumococcal serotypes 22 F and 33 F: a systematic review and meta-analysis with meta-regression.

backgroundStreptococcus pneumoniae remains a major cause of morbidity and mortality worldwide, particularly among children and older adults. Although 13-valent pneumococcal conjugate vaccine (PCV13) significantly reduced the burden of pneumococcal disease, non-PCV13 serotypes such as 22 F and 33 F continue to cause invasive pneumococcal disease (IPD). PCV15 was developed to address this gap by including serotypes 22 F and 33 F.

methodsFollowing PRISMA guidelines, a comprehensive literature search was conducted across multiple databases through March 2024. Randomized controlled trials (RCTs) comparing PCV15 and PCV13 were included. Primary outcomes included IgG geometric mean concentrations (GMCs) and opsonophagocytic activity geometric mean titers (OPA GMTs) for serotypes 22 F and 33 F.

resultsNineteen RCTs (n = 16,046) were included. PCV15 demonstrated significantly higher immunogenicity than PCV13 for serotypes 22 F and 33 F across most age and dose subgroups. For IgG GMCs, pooled mean differences (MDs) for serotype 22 F were 6.34 (95% CI 5.13-7.56; I²=97%) in infants, 10.09 (95% CI 6.06-14.13; I²=92%) in children, and 3.19 (95% CI 2.01-4.36; I²=96%) in adults. For serotype 33 F, MDs were 2.40 (95% CI 1.52-3.28; I²=99%), 4.27 (95% CI 3.74-4.80; I²=0%), and 6.81 (95% CI 5.10-8.52; I²=93%), respectively. OPA GMTs also favored PCV15 for serotype 22 F after both single-dose (MD = 1.55, 95% CI 0.69-2.41; I²=99%) and three-dose schedules (MD = 1.66, 95% CI 1.24-2.08; I²=87%), while for serotype 33 F, superiority was observed only with three doses (MD = 0.98, 95% CI 0.56-1.39; I²=90%). PCV15 was associated with higher rates of injection-site adverse events (RR = 1.08, 95% CI 1.03-1.11), whereas systemic adverse events were comparable between groups (RR = 1.03, 95% CI 1.00-1.06). Meta-regression identified a significant negative association between age and IgG GMC 22 F (β=-0.061, 95% CI -0.096 to -0.025; p ≤ 0.001). Certainty of evidence ranged from low to moderate according to GRADE assessment, primarily limited by inconsistency across studies.

conclusionPCV15 demonstrated significantly higher immunogenicity against serotypes 22 F and 33 F than PCV13 across most age and dose subgroups while maintaining a generally comparable safety profile. These findings support the immunogenic advantage of PCV15 for the additional serotypes included in the vaccine; however, studies evaluating clinical effectiveness are needed to determine whether these immunological differences translate into reductions in pneumococcal disease.