P-617. Estimating Pediatric Breakthrough Disease from Pneumococcal Vaccines in France
Authors: Bakker Kevin , Oidtman Rachel , Meleleo Giulio , Velentgas Priscilla , Klinker Kenneth , Banniettis Natalie , Feemster Kristen A , Weaver Jessica 
Published: January 2025

Abstract

Background
In France, effective pneumococcal conjugate vaccines (PCVs) and the high vaccine coverage rate (VCR) of 95% have led to a substantial decline in pediatric invasive pneumococcal disease (IPD) incidence. PCV13 is currently used in a 2+1 dosing regimen; PCV15 and PCV20 are expected to be introduced soon. Breakthrough IPD (bIPD), defined as fully vaccinated individuals who develop vaccine type IPD, persists for some PCV13 serotypes (STs). As ST-specific immune responses decrease with increased PCV valency, understanding the potential impact of PCV15 and PCV20 on PCV13 STs bIPD is important.
IPD Breakthrough disease incidence per 100,000 children under two years of age.

Methods
We evaluated the expected impact of PCV15 in a 2+1 regimen, or PCV20 in either a 2+1 or 3+1 regimen on PCV13 ST bIPD incidence in children &lt; 2 years of age over 5 and 10 years using a compartmental dynamic transmission model. The model incorporated historical PCV introductions and calibrated age- and ST-specific IPD data spanning 2000-2019. Predicted ST-specific vaccine effectiveness (VE) for PCV15 and PCV20 were used1,2. Incidence of bIPD was evaluated across 3 ST groupings: PCV7 STs, PCV13-non-ST3 STs, and ST3. VCRs were maintained at 95% in the model. Results were compared to 2019 IPD incidence.

Results
Using previously published ST-specific VE predictions, routine use of PCV15 in children led to fewer PCV13 ST bIPD cases than use of PCV20. PCV15 reduced bIPD incidence in all 3 ST groups (-30% to -87%, Table 1). The introduction of PCV20 in a 2+1 or 3+1 regimen resulted in more bIPD cases from PCV7 and PCV13-non-ST3 STs. ST3 bIPD was maintained at current levels in a 2+1 regimen but decreased with PCV20 in a 3+1 regimen.

Conclusion
Using published predicted VEs, implementation of PCV20 in a 2+1 or 3+1 regimen led to a substantial increase in bIPD incidence of PCV7 and PCV13 non-ST3 STs relative to currently used PCV13 2+1 regimen. PCV15 in a 2+1 regimen reduced bIPD incidence across all ST groups, with the largest impact on ST3. As higher-valent PCVs are introduced, the impact of their reduced ST-specific immune responses, and therefore lower predicted VE on pediatric PCV13 STs, should be weighed against the benefits of additional ST coverage.
1Ryman J, et al. Expert Rev Vaccines. 2024;23(1):60-68.
2Ryman J, et al. Expert Rev Vaccines. 2024;23(1):467-473.

Disclosures
Kevin Bakker, PhD, Merck & Co., Inc.: Grant/Research Support|Merck & Co., Inc.: Stocks/Bonds (Public Company) Rachel Oidtman, PhD, Merck & Co., Inc.: Full time employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Giulio Meleleo, PhD, Merck & Co., Inc.: Vendor Priscilla Velentgas, PhD, Merck & Co., Inc., Rahway, NJ, USA: Grant/Research Support|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Kenneth Klinker, PharmD, Merck & Co., Inc., Rahway, NJ, USA: Grant/Research Support|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Natalie Banniettis, MD, Merck & Co., Inc., Rahway, NJ, USA: Grant/Research Support|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Kristen A. Feemster, MD, MPH, MSHPR, FAAP, Merck & Co., Inc., Rahway, NJ, USA: Grant/Research Support|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Jessica Weaver, PhD, MPH, Merck & Co. Inc.: Employment|Merck & Co. Inc.: Stocks/Bonds (Public Company)