Comparative Immunogenicity of 15-Valent and 20-Valent Pneumococcal Conjugate Vaccines: Evidence from a Network Meta-Analysis
1
Department of Medicine and Surgery, University of Perugia, Perugia, Italy
2
Graduate School of Health Economics and Management (ALTEMS), Università Cattolica del Sacro Cuore, Rome, Italy
3
Prevention Department Hygiene and Public Health Service, ASL Roma 1, Rome, Italy
4
Department of Medical Direction, Hospital of Perugia, Perugia, Italy
5
Department for the Promotion of Human Sciences and Quality of Life, San Raffaele University of Rome, Rome, Italy
6
Unit of Clinical and Molecular Epidemiology, RCCS San Raffaele Rome, Rome, Italy
Popul. Med. 2026;8(Supplement Supplement 1):
ABSTRACT
INTRODUCTION:
Streptococcus pneumoniae is a major global cause of morbidity and mortality in adults, disproportionately affecting older individuals and those with underlying conditions. After the worldwide rollout of pneumococcal conjugate vaccines (PCVs) (e.g., PCV7 and subsequently PCV10/PCV13), the latest-generation higher-valent PCVs, 20-valent (PCV20) and 15-valent (PCV15), were developed to address residual disease burden and serotype replacement; however, no head-to-head trials directly comparing the PCV20 and PCV15 vaccines in adults and elderly are currently available. As comparative evidence is essential to inform effective vaccination policies within diverse epidemiological contexts, we performed a systematic review and network meta-analysis.
METHODS:
The work followed PRISMA-NMA guidelines. Randomized controlled trials enrolling adults (≥18 years) and evaluating PCV20 or PCV15 were identified through searches of PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov. The primary outcome was serotype-specific opsonophagocytic activity (OPA) geometric mean titers at 30 days. The ratios of means were used in a frequentist network meta-analysis with PCV13 as the common comparator. Prespecified age-stratified analyses (18–49, ≥50, ≥60 years) were carried out to explore potential effect modification by age.
RESULTS:
Seventeen trials met inclusion criteria; nine contributed quantitative OPA data for 15 serotypes. No direct adult comparison between PCV20 and PCV15 was available. Overall, PCV20 elicited comparable or lower OPA responses than PCV15 for most shared serotypes, with statistically significant differences favoring PCV15 for several clinically important serotypes, including serotype 3. PCV20 showed superiority only for serotype 4 and in younger age groups. Age-stratified analyses indicated more frequent advantages for PCV15 in older adults.
CONCLUSIONS:
While PCV20 expands serotype coverage, PCV15 demonstrates higher immunogenicity for shared serotypes, particularly in older adults. These findings suggest that public health decisions in respect to pneumococcal vaccination should rely on local serotype epidemiology, population age structure, and equity considerations. Furthermore, real-world studies on the relative effectiveness remain a priority.
Streptococcus pneumoniae is a major global cause of morbidity and mortality in adults, disproportionately affecting older individuals and those with underlying conditions. After the worldwide rollout of pneumococcal conjugate vaccines (PCVs) (e.g., PCV7 and subsequently PCV10/PCV13), the latest-generation higher-valent PCVs, 20-valent (PCV20) and 15-valent (PCV15), were developed to address residual disease burden and serotype replacement; however, no head-to-head trials directly comparing the PCV20 and PCV15 vaccines in adults and elderly are currently available. As comparative evidence is essential to inform effective vaccination policies within diverse epidemiological contexts, we performed a systematic review and network meta-analysis.
METHODS:
The work followed PRISMA-NMA guidelines. Randomized controlled trials enrolling adults (≥18 years) and evaluating PCV20 or PCV15 were identified through searches of PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov. The primary outcome was serotype-specific opsonophagocytic activity (OPA) geometric mean titers at 30 days. The ratios of means were used in a frequentist network meta-analysis with PCV13 as the common comparator. Prespecified age-stratified analyses (18–49, ≥50, ≥60 years) were carried out to explore potential effect modification by age.
RESULTS:
Seventeen trials met inclusion criteria; nine contributed quantitative OPA data for 15 serotypes. No direct adult comparison between PCV20 and PCV15 was available. Overall, PCV20 elicited comparable or lower OPA responses than PCV15 for most shared serotypes, with statistically significant differences favoring PCV15 for several clinically important serotypes, including serotype 3. PCV20 showed superiority only for serotype 4 and in younger age groups. Age-stratified analyses indicated more frequent advantages for PCV15 in older adults.
CONCLUSIONS:
While PCV20 expands serotype coverage, PCV15 demonstrates higher immunogenicity for shared serotypes, particularly in older adults. These findings suggest that public health decisions in respect to pneumococcal vaccination should rely on local serotype epidemiology, population age structure, and equity considerations. Furthermore, real-world studies on the relative effectiveness remain a priority.
| eISSN: | 2654-1459 |
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