Pneumococcal serotypes missing prespecified efficacy threshold in immunogenicity trials: real-world evidence from...

Area of Science:

• Immunology
• Vaccinology
• Epidemiology

Background:

• Pneumococcal conjugate vaccines (PCV13 and PCV10) showed missed non-inferiority for specific 7-valent (PCV7) serotypes in trials.
• This highlights a potential discrepancy between trial immunogenicity and population-level disease impact.

Purpose of the Study:

• To investigate population-level invasive pneumococcal disease (IPD) case trends for PCV7 serotypes that missed or met non-inferiority criteria in trials.
• To compare the real-world effectiveness of PCV13 and PCV10 against specific serotypes across different age groups.

Main Methods:

• Analysis of national IPD surveillance data from nine countries (six PCV13, three PCV10) for 8 years post-vaccine introduction.
• Extracted IPD case counts for specific PCV7 serotypes categorized by non-inferiority trial status.
• Stratified data by age groups (<5 and ≥5 years) to observe serotype trends.

Main Results:

• IPD cases for PCV7 serotypes that missed non-inferiority consistently decreased or remained suppressed across all analyzed countries and ages.
• Similar suppression trends were observed for PCV7 serotypes that met non-inferiority in children under 5 years.
• Paradoxically, IPD cases for certain serotypes (4 and 19F) increased in individuals aged 5 years and older in Canada, Italy, and the US.

Conclusions:

• Higher-valent PCVs (PCV13/PCV10) demonstrate effectiveness in suppressing targeted pneumococcal serotypes in real-world settings, irrespective of immunogenicity trial outcomes.
• Non-inferiority criteria in immunogenicity trials may not accurately predict the population-level impact of pneumococcal conjugate vaccines.