The relative immunogenicity of 20-valent and 15-valent pneumococcal conjugate vaccines: A systematic review and network meta-analysis

Higher-valent pneumococcal conjugate vaccines (PCV) may reduce adult pneumococcal disease, but no head-to-head trials compare PCV20 vs. PCV15 in adults. We synthesized serotype-specific immunogenicity from randomized controlled trials using a network meta-analysis via the common comparator PCV13. PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov were searched for trials enrolling adults (≥18 y) and evaluating PCV20 or PCV15. The primary endpoint was opsonophagocytic activity (OPA) geometric mean titers (GMTs) at 30 d, summarized as ratios of means on the log scale. Heterogeneity/inconsistency were assessed and prespecified age-stratified analyses were performed where possible. Seventeen trials met inclusion criteria but nine contributed OPA data for 15 serotypes. Across most shared serotypes, PCV20 elicited comparable or lower OPA responses than PCV15, with significantly higher responses for PCV15 for several serotypes, including 3. PCV20 exceeded PCV15 only for serotype 4. Age-stratified results suggested greater relative advantages for PCV15 in older adults. Direct comparative and real-world effectiveness studies are needed.