Related Experiment Video

Updated: May 11, 2026

Experimental Human Pneumococcal Carriage

Experimental Human Pneumococcal Carriage

Published on: February 15, 2013

PCV13-Serotype Breakthrough Pneumococcal Disease in Infants Receiving High-Valency Conjugate Vaccines:

Kevin M Bakker¹, Rachel J Oidtman¹, Natalie Banniettis²

¹Health Economic and Decision Sciences, Merck & Co., Inc., Rahway, NJ, USA.

Infectious Diseases and Therapy

|March 19, 2025

Insights

Pneumococcal conjugate vaccine (PCV) models show PCV15 reduces breakthrough invasive pneumococcal disease (bIPD) in infants. PCV20 may increase bIPD cases, particularly from PCV7 serotypes with a 3+1 regimen.

Area of Science:

Immunology
Vaccinology
Epidemiology

Background:

Pneumococcal conjugate vaccines (PCVs) are evolving to cover more serotypes.
Increased valency may reduce vaccine immunogenicity, potentially leading to breakthrough disease.

Purpose of the Study:

To mathematically model the impact of PCV15 versus PCV20 on breakthrough invasive pneumococcal disease (bIPD) in French infants.
To compare bIPD incidence across different serotype classes (PCV7, PCV13-nonPCV7-nonST3, ST3) under various vaccination regimens.

Main Methods:

Utilized a mathematical model calibrated with IPD data from 2000-2019 in France.
Predicted serotype-specific vaccine effectiveness for PCV15 and PCV20.
Evaluated bIPD incidence in infants (0-12 months) comparing PCV15 and PCV20 (2+1 or 3+1 regimens) against 2019 IPD levels.

Main Results:

PCV15 (2+1 regimen) resulted in fewer bIPD cases in infants compared to PCV20 (any regimen), particularly for ST3 serotypes.
PCV15 reduced bIPD incidence across all evaluated serotype classes (-28% to -89%).
PCV20 increased bIPD cases from PCV7 serotypes (+65% to +350%) and, in a 2+1 regimen, also increased PCV13-nonPCV7-nonST3 and ST3 cases.

Conclusions:

PCV15 in a 2+1 regimen is projected to decrease bIPD incidence for all PCV13 serotypes in infants.
PCV20 with a 2+1 regimen may significantly increase infant bIPD due to PCV13 serotypes.
PCV20 with a 3+1 regimen might lead to a resurgence of bIPD caused by PCV7 serotypes in infants.

Read full analysis

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.

Keywords:

Breakthrough disease Dynamic transmission model Infant Pneumococcal infections Pneumococcal vaccines

More Related Videos

Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria

Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria

Published on: February 23, 2014

Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43

Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43

Published on: September 11, 2020

Related Concept Videos

Pneumonia I: Introduction

Pneumonia I: Introduction

Pneumonia is an acute respiratory infection that targets the lungs, specifically the alveoli. These tiny air sacs, essential for oxygen exchange, become engorged with pus and fluid, severely hindering breathing, decreasing oxygen absorption, and causing significant pain and discomfort during respiration.
Risk Factors
Various factors influence the likelihood of developing pneumonia. Age plays a crucial role, with infants, children under two, and individuals over 65 at increased risk due to their...

Pneumonia II: Pathophysiology

Pneumonia II: Pathophysiology

The pathophysiology of pneumonia involves the following steps:

Pneumonia IV: Management

Pneumonia IV: Management

The treatment of pneumonia varies based on its severity and the causative pathogen. Here is a structured approach to managing pneumonia, integrating pharmaceutical and supportive care strategies.
Bacterial Pneumonia Treatment
For bacterial pneumonia, antibiotics serve as the cornerstone of therapy. Initial treatment often begins with empirical antibiotics, tailored to the anticipated causative organism and adjusted based on culture results. Key antibiotic choices include:

Pneumonia V: Nursing management and Prevention

Pneumonia V: Nursing management and Prevention

Nursing management of pneumonia involves promoting airway patency, facilitating rest and conserving energy, encouraging fluid intake, maintaining nutrition, and educating patients.
The nurse must practice strict medical asepsis and adhere to infection control guidelines to minimize healthcare-associated infections.
Enhance airway patency
Position the patient correctly to facilitate drainage of the affected lung segments. Manual or mechanical percussion and vibration can also be employed.

Bacterial Meningitis I: Introduction

Bacterial Meningitis I: Introduction

Bacterial meningitis is a severe, life-threatening inflammation of the meninges, particularly the pia mater and arachnoid mater, affecting the subarachnoid space, ventricles, and cerebrospinal fluid (CSF). If untreated, it can lead to significant neurological complications or death.Causative AgentsCommon pathogens vary with age and immune status. In adults, major organisms include Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Streptococcus agalactiae (group B...

Pneumonia I: Introduction

Pneumonia I: Introduction

Pneumonia is an infection of the lower respiratory tract that leads to inflammation of the lung parenchyma, often resulting in the accumulation of inflammatory exudate in the alveoli and airways. Unlike the watery, low-protein fluid exudate in pulmonary edema, the exudate in this case is a thick fluid rich in immune cells, proteins, and debris produced during infection and inflammation.This impairs gas exchange and can lead to consolidation of lung tissue. The infection may be caused by a...

Articles linked to this work by shared authors, journal, and citation graph.

Projected epidemiological impact of lowering the adult pneumococcal vaccination age from 60 to 50 years in Germany.

Human vaccines & immunotherapeutics·2026

Healthcare resource utilization and cost of invasive pneumococcal disease, pneumonia, and acute otitis media in commercially and medicaid-insured children by risk group in the United States, 2018 to 2023.

Pneumonia (Nathan Qld.)·2026

Incidence of Invasive Pneumococcal Disease in US Children by Risk Group, 1998-2023.

Journal of the Pediatric Infectious Diseases Society·2026

Health impact and cost-effectiveness analysis of introducing a national immunization program with 21-valent versus 20-valent pneumococcal conjugate vaccines for adults ≥65 years of age in Denmark.

Expert review of pharmacoeconomics & outcomes research·2026

From survey to solutions: Tackling diversity and inclusion gaps through an inclusion task force.

Epidemics·2026

Epidemiological impact of a 20- or 21-valent pneumococcal conjugate vaccine in the Japan adult population: insights from a dynamic transmission model.

Expert review of vaccines·2026

See all related articles