PCV13-Serotype Breakthrough Pneumococcal Disease in Infants Receiving High-Valency Conjugate Vaccines: Population-Level Modeling in France.

Abstract

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.