Introduction: Pneumococcal conjugate vaccines (PCVs) have been increasing in valency to protect against a larger number of serotypes; however, the addition of serotypes has come at the cost of reduced immunogenicity, which may lead to breakthrough disease.
Methods: This study used a mathematical model to evaluate the impact of introducing routine vaccination with either PCV15 or PCV20 on breakthrough invasive pneumococcal disease (bIPD) incidence associated with PCV13 serotypes in infants aged 0-12 months in France. The model incorporated historical PCV introductions and calibrated age- and serotype-specific IPD data spanning 2000-2019. Serotype-specific vaccine effectiveness for PCV15 and PCV20 was predicted based on previously published analyses. The incidence of bIPD was evaluated across three serotype classes: PCV7 (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F), PCV13-nonPCV7-nonST3 (serotypes 1, 5, 6A, 7F, and 19A), and ST3 (serotype 3). Results were compared to IPD incidence in 2019.
Results: Twenty years following introduction into the childhood immunization program, the routine use of PCV15 in a 2 + 1 regimen led to fewer PCV13-nonPCV7-nonST3-associated bIPD cases in infants than the use of PCV20 in either a 2 + 1 or 3 + 1 regimen. PCV15 reduced bIPD incidence in all three serotype classes (- 28% to - 89%) in infants, with the largest impact on ST3. PCV20 in both regimens resulted in more bIPD cases from PCV7 serotypes (+ 65% to + 350%), while PCV13-nonPCV7-nonST3 and ST3 bIPD cases increased in a 2 + 1 regimen (+ 28% and + 6%, respectively) but decreased in a 3 + 1 regimen (- 23% and - 30%, respectively), in infants.
Conclusions: Implementation of PCV15 in a 2 + 1 regimen could reduce bIPD incidence due to all PCV13 serotypes in infants, whereas PCV20 in a 2 + 1 regimen may lead to substantial increases in bIPD cases from PCV13 serotypes in infants. PCV20 in a 3 + 1 regimen could potentially lead to a resurgence of bIPD from PCV7 serotypes in infants.
Keywords: Breakthrough disease; Dynamic transmission model; Infant; Pneumococcal infections; Pneumococcal vaccines.
Pneumococcal conjugate vaccines (PCVs) have been increasing in valency to protect against a larger number of serotypes; however, the addition of serotypes has come at the cost of reduced immunogenicity, which may lead to breakthrough disease. Currently, a 13-valent PCV (PCV13) is used routinely in infants via a 2 + 1 dosing regimen in France, however, two novel higher valency PCVs (PCV15 in a 2 + 1 and 3 + 1 dosing regimen and PCV20 in a 3 + 1 dosing regimen) have more recently been recommended for use in France. This study used a mathematical model to evaluate the impact of introducing routine vaccination with either PCV15 or PCV20 on breakthrough invasive pneumococcal disease (bIPD) incidence associated with PCV13 serotypes in infants aged 0–12 months in France. The incidence of bIPD was evaluated across three serotype classes: PCV7 (serotypes 4, 6B, 9 V, 14, 18C, 19F, and 23F), PCV13-nonPCV7-nonST3 (serotypes 1, 5, 6A, 7F, and 19A), and ST3 (serotype 3). Results were compared to invasive pneumococcal disease incidence in 2019. Twenty years following introduction into childhood immunization program, the routine use of PCV15 in a 2 + 1 regimen led to fewer PCV13-nonPCV7-nonST3-associated bIPD cases in infants than the use of PCV20 in either a 2 + 1 or 3 + 1 regimen, whereas PCV20 in both regimens (2 + 1 and 3 + 1) resulted in more bIPD cases from PCV7 serotypes, while PCV13-nonPCV7-nonST3 and ST3 bIPD cases increased in a 2 + 1 regimen but decreased in a 3 + 1 regimen in infants.
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