Potential serotype-specific effectiveness against IPD of pneumococcal conjugate vaccines V114 and PCV20 in children given a 2+1 dosing regimen

ABSTRACT

Background

Next generation, higher valency pneumococcal conjugate vaccines (PCVs) are assessed and licensed by comparing the immune response across serotypes shared with the PCVs that are standard of care for prevention of pneumococcal disease.

Methods

Using a previously qualified method we predicted the serotype-specific vaccine effectiveness (VE) against invasive pneumococcal disease of V114 and PCV20 for the serotypes shared with PCV13 in an EU, Russian, and Australian pediatric population that is recommended to receive a 2 + 1 dosing regimen.

Results

The estimated protective antibody concentrations ranged from 0.03 (serotype 23F) to 1.49 µg/mL (serotype 19F). Predicted VE values for V114 ranged from 79% (serotype 5) to 100% (serotype 23F). V114 had comparable effectiveness to PCV13 for all but one of shared serotypes, with predicted higher effectiveness (in V114) against serotype 3 (93% vs. 65%). Predicted VE values for PCV20 ranged from 47% (serotype 3) to 91% (serotype 14). PCV20 predicted VE was lower than PCV13’s for serotypes 4, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A.

Conclusions

Predicted serotype-specific VE values suggest that, with a 2 + 1 dosing regimen, V114 will have greater effectiveness than PCV20 against PCV13 serotypes, particularly for the still-prevalent serotype 3. Real-world VE studies will ultimately provide clarity on the effectiveness of novel PCVs and support further confidence in and/or improvements to modeling efforts.

Plain Language Summary

Pediatric pneumococcal conjugate vaccines (PCVs) were first introduced in Europe in the early 2000s and their incorporation into national immunization programs has helped decrease the incidence of invasive pneumococcal disease (IPD) in Europe and globally. However, some IPD persists, due both to the emergence of non-vaccine pneumococcal serotypes and to the persistence of certain vaccine-targeted serotypes. Higher valency vaccines have been developed to help prevent IPD arising from these serotypes. The goal of the present study is to employ a previously developed model to predict the serotype-specific vaccine effectiveness of higher valency PCVs in a pediatric population that is recommended to receive a 2 + 1 dosing schedule.

KEYWORDS:

• Antibodies
• child
• immunization schedule
• modeling and simulation
• pharmacometrics
• pneumococcal vaccines
• protective concentration
• streptococcus pneumoniae

Declaration of interest

All authors were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. at the time of the study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium for their review work. A reviewer on this manuscript has disclosed that they are a member of the WHO SAGE Working Group on Pneumococcal Vaccines, the JCVI Pneumococcal Vaccines Working Group and the Standing Committee on Vaccination.

Author contributions

Conception and design: JR, JRS, NB, TW, JW. Analysis and interpretation of the data: JR, JRS, NB, TW, MA, KLY, JW. Drafting the manuscript: JR, NB, TW, KLY, JW. Revising the manuscript for intellectual content: JR, JRS, NB, TW, MA, KLY, JW. All authors approve the final version of the manuscript and agree to be accountable for all aspects of the work.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article or its supplementary materials.

Acknowledgments

The authors thank Melissa Stauffer, PhD, in collaboration with ScribCo, for medical writing assistance.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2024.2335323

Additional information

Funding

This study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.