Introduction Pneumococcal conjugate vaccines (PCVs) were first introduced in the paediatric United Kingdom (UK) immunisation programme in 2006 which led to significant declines in invasive pneumococcal disease (IPD) caused by targeted serotypes. Although paediatric PCVs provide some indirect protection to adults, a significant IPD burden remains in older adults. Here, we compared three adult (65+ years-old) and risk group (2–64-year-old) vaccination scenarios, namely a continuation of the status quo with PPSV23 vaccination, using the recently licensed-in-adults PCV20, or using the new adult-focused 21-valent PCV, V116. Methods A population-level compartmental dynamic transmission model (DTM) was adapted to the UK setting. The model described Streptococcus pneumoniae carriage transmission dynamics and disease progression in the presence of age- and serotype-specific pneumococcal vaccines. We calibrated the DTM to age- and serotype-specific IPD data in the UK and used the model to make projections under the different adult vaccination scenarios while keeping PCV13 immunisation in children. Results The calibrated model yielded reasonable parameter values and model fits that closely matched observed IPD dynamics. Among 65+ year-olds, 10-year model projections predicted that the routine use of V116 would reduce IPD incidence by 15.5%, while PCV20 would reduce IPD incidence by 8.9% and the continued use of PPSV23 would increase incidence by 3.83%. There was a notable decrease in IPD incidence in the serotypes unique to V116. In the serotypes included in PCV20 but not V116, the model did not predict a resurgence of IPD. Conclusions Projections revealed that in adults, V116 led to significantly greater reductions in IPD in the 65+ year-old population compared with PCV20 or PPSV23.

Background/Objectives: The clinical impact of replacing the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the vaccination of older (≥60 years) and at-risk German adults with either the 20-valent (PCV20) or 21-valent (V116) pneumococcal conjugate vaccine (PCV) was evaluated. Methods: An age- and serotype-specific transmission model was adapted to Germany to evaluate the impact of V116 versus PCV20 vaccination on pneumococcal disease (PD) incidence, including invasive pneumococcal disease (IPD) and inpatient and outpatient non-bacteremic pneumococcal pneumonia, over 10 years. A reference strategy (PPSV23 vaccination at a constant 30% vaccine coverage rate (VCR)) was compared against eight strategies varying by PCV (PCV20 vs. V116), VCR (30% vs. 60%), with or without the PCV revaccination of previously PPSV23-vaccinated adults (0% vs. 50% revaccination). Results: Vaccination with PCV20 and V116 initially decreased PD incidence, but incidence returned to pre-vaccine levels after five and eight years, respectively. Increasing the VCR to 60% prevented this resurgence. At a 10-year time horizon, V116 with 30% VCR reduced IPD cases by 9%, inpatient NBPP cases by 10%, and outpatient NBPP cases by 7% compared to the reference strategy. PCV20 with 30% VCR reduced these cases by 6%, 5%, and 4%, respectively. Increasing the VCR to 60% and revaccinating 50% of previously PPSV23-vaccinated adults further reduced IPD cases by 14% and 13% for V116, and by 9% and 9% for PCV20. Conclusions: Increasing the vaccination coverage rate to 60% and strategically revaccinating previously PPSV23-vaccinated adults significantly enhanced the effectiveness of pneumococcal vaccines, with V116 showing greater overall reductions in disease incidence compared to PCV20 or PPSV23.

Indirect effects refer to the population-level effects of vaccination on vaccinated and unvaccinated individuals, including herd protection, serotype replacement, and age shifts, which can substantially impact the real-world effectiveness of vaccination programs. Despite their importance, most economic evaluations omit indirect effects, likely owing to the complexity of underlying mechanisms, data limitations, and difficulties in disentangling confounding factors. Static models and dynamic transmission models (DTMs) are two common approaches for incorporating indirect effects in economic evaluations. Static models rely on simplified assumptions and readily available data but often overlook the temporal and population-level dynamics of disease transmission. In contrast, DTMs account for complex factors (e.g., population mixing, serotype competition, and long-term epidemiological changes) but require more complex model structure and extensive data. In this article, we illustrate the applications, strengths, and limitations of these two modeling approaches through case studies. We demonstrate how choices of model structure and assumptions, data sources, and parameter estimation methodologies can influence projected epidemiological and economic outcomes, sometimes leading to divergent conclusions. While international guidelines increasingly recognize the importance of including indirect effects in economic evaluations, limited methodological guidance from National Immunization Technical Advisory Groups (NITAGs) and health technology assessment (HTA) bodies continues to hinder consistent implementation. This paper advocates for a collaborative effort among stakeholders to generate high-quality surveillance data and establish guidelines for methodological considerations to model indirect effects. Such efforts will improve the accuracy of epidemiological and economic assessments of vaccination programs and strengthen evidence-based decision-making in public health.

Background/Objectives: Pneumococcal conjugate vaccines (PCVs) were first introduced in the pediatric UK National Immunization Programme (NIP) in 2006 and subsequently led to a significant decline in invasive pneumococcal disease (IPD). In 2020, the UK NIP reduced the pediatric PCV dosing schedule from two infant doses and one toddler dose (2 + 1) to one infant dose and one toddler dose (1 + 1). This analysis evaluated the public health impact of pediatric vaccination with PCV15 versus PCV13 under a 1 + 1 schedule. Methods: A population-level compartmental model was previously adapted to the UK setting. The impact on the IPD incidence of vaccination with PCV15 versus PCV13 under a 1 + 1 schedule was evaluated over a 20-year time horizon. The uncertainty regarding the vaccine efficacy (VE) of PCV13 and PCV15 under a 1 + 1 schedule was investigated through a probabilistic sensitivity analysis, i.e., the PCV VE under a 1 + 1 schedule was assumed to be 0–24% lower than the PCV VE under a 2 + 1 schedule. Results: Relative to the initial IPD incidence, vaccination with PCV13 and PCV15 under a 1 + 1 schedule resulted in the IPD incidence in children <2 years old increasing by 11.1% (95% region: 8.4–14.5%) and 3.5% (0.2–7.7%), respectively, over the time horizon. At the end of the time horizon, in the overall population, PCV15 would lead to a 6.0% lower IPD incidence than PCV13 (10.70 IPD cases per 100,000 versus 11.38 per 100,000, respectively). Conclusions: Switching from PCV13 to PCV15 for routine pediatric vaccinations under the 1 + 1 dosing schedule in the UK led to a lower IPD incidence in both the pediatric and overall populations.

Introduction: In 2020 the UK National Immunization Programme reduced the pediatric dosing schedule for pneumococcal vaccination with PCV13 from 2 doses in infancy followed by a toddler dose (2+1 schedule) to 1 dose in infancy followed by a toddler dose (1+1 schedule). Real world data on vaccine effectiveness (VE) against invasive pneumococcal disease (IPD) under the reduced dosing schedule is not available, nor is data on VE associated with higher valency vaccines, including PCV15. This analysis investigates changes in projected disease outcomes associated with potential reductions in VE against IPD with PCV13 and PCV15 under the 1+1 reduced dosing schedule. Methods: A previously published dynamic transmission model was employed to project population-level IPD incidence under 1+1 pneumococcal vaccination dosing of children <2 years old with two different vaccine formulations, with maintenance of current adult and at-risk vaccination programs, under a range of assumptions regarding reduction of VE against IPD, over a 20-year timeline following the switch to the 1+1 schedule. A probabilistic sensitivity analysis was performed to evaluate the sensitivity of model outcomes to potential changes in VE against IPD. Results: Relative to 2019 estimates, overall IPD incidence was predicted to increase over the time horizon for both PCV13 and PCV15 programs, however vaccination with PCV15 was estimated to lead to a smaller increase over all age groups than vaccination with PCV13. Both vaccine formulations led to projected decreases in IPD attributed to common PCV13/PCV15 serotypes in children <2 years old. Sensitivity analyses reflect results were robust to potential changes in VE against IPD. Conclusions: The current analysis predicts switching the routinely administered pediatric pneumococcal vaccine from PCV13 to PCV15 within the UK’s 1+1 dosing schedule would not only reduce IPD in the pediatric population but would also lead to population-level reductions in IPD due to indirect protection.