Optimizing the timing of one or two doses of pneumococcal conjugate vaccines in older adults in the United States: a modeling study

  1. Deus Thindwa
  2. Anabelle Wong
  3. Matthieu Domenech de Cellès
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Abstract

Background

Older adults have a high burden of pneumococcal disease. Pneumococcal conjugate vaccines (PCVs) are effective in reducing disease risk. Recent changes to lower recommended age of pneumococcal vaccination among PCV-naïve adults by the United States (US) Centers for Disease Control and Prevention (CDC) raises important questions on the optimal age of pneumococcal vaccination, as well as revaccination later in life when immunogenic responses to vaccination declines and disease activity peaks. We aimed to estimate the optimal age(s) and impact of a single dose and two-dose series of pneumococcal vaccination in adults ≥50 years-old (y) in the US.

Methods and findings

Age– and vaccine-serotype-specific IPD cases from the CDC’s Active Bacterial Core surveillance (ABCs) system among adults ≥50y in 2022 were combine with age and race demographic estimates, status of prior PCV use in adult population, vaccine effectiveness (VE), and waning VE dynamics in a cohort model of vaccine impact. Of the 12.8 million ABCs residents aged ≥50y, 52.4% were aged ≥65y. Black adults in age band 50-64y accounted for 60.2% of the total Black adult population compared to 51.8% of non-Black adults among the total non-Black adult population. A total of 1,557 IPD cases were reported across all ABCs sites; 349 cases in Black (N=1.6 million) and 1,208 cases in non-Black (N=11.2 million) adults. Cases caused by serotypes covered in higher-valency PCV20, PCV21 and PCV31, respectively, accounted for 52.7%, 74.9% and 87.9% of all IPD cases, and these proportions were similar between Black and non-Black adults. The optimal age of a single-dose higher-valency PCV was at 60y or 65y in overall population; earlier at 60y in Black adults compared to 65y in non-Black adults if initial VE was not influenced by age of vaccination. The optimal age shifted to 50y or 60y in overall population; earlier at 50y in Black adults compared to 60y in non-Black adults if initial VE was lower at higher age of vaccination. For maximum impact, a two-dose strategy showed that if the first dose is given at ≥65y, the second dose should be given at 5 years after initial dose, and if the first dose is given between 50-64y, the second dose should be given at 10 or 15 years after initial dose, irrespective of VE assumptions or race group.

Conclusions

Age of vaccination with a single dose of PCV that prevents maximum IPD cases is generally at 60y or 65y, and earlier among underserved populations, reflecting CDC’s new changes to lower age of vaccination. Optimal age of vaccination with a second dose of PCV is influenced by the timing of the first dose. Our results are driven by population age structure, age-specific IPD risk, VE dependency on age and waning VE uncertainty. These findings could help inform cost-effective planning and future age– and risk-based PCV recommendations.

Author summary

Why was this study done?

  • Disparities in pneumococcal disease burden are widespread among adults aged ≥50 years-old in the United States across demographic groups

  • This study was conducted to explore the optimal age of vaccination with a single dose of higher-valency pneumococcal conjugate vaccine (PCV) in older adults

  • This study was conducted to evaluate the potential benefits of a booster dose with a higher-valency pneumococcal conjugate vaccine and the optimal timing of that dose

What did the researchers do and find?

  • We conducted a modeling study using a cohort model and age– and serotype-specific invasive pneumococcal disease (IPD) case data from the Centers for Disease Control and Prevention (CDC)’s large Active Bacterial Core surveillance (ABCs) system, stratified by epidemiologic and vaccination variables

  • The age of vaccination with a single dose of higher-valency PCV that averted most cases was overall at 60y or 65y (60y for Black adults, 65y for non-Black adults) for age-independent initial VE, or overall at 50y or 60y (50y for Black adults, 60y for non-Black adults) for age-dependent initial VE.

  • Optimal timing of a second dose of higher-valency PCV was at 5 years after administration of initial dose in late adulthood (≥65y) or at 10 or 15 years after administration of initial dose in early adulthood (50-64y)

What do these findings mean?

  • Age of vaccination with a single dose of higher-valency PCV that averts most cases is earlier among Black than non-Black adults

  • Appropriate timing of a second dose of PCV can improve the management of pneumococcal disease

  • Studies are needed to provide evidence of long-term changes in PCV effectiveness against pneumococcal disease among older adults

Article activity feed

  1. Version published to 10.1101/2025.10.24.25338736 on medRxiv