ESCMID Global 2025: Real-world effectiveness of PCV20 against IPD and ACP among older adults in the US

25 Jun 2025 byMs. Amanda Miles, Vaccines Real World Evidence Scientist of Pfizer Vaccines, New York, New York, US
ESCMID Global 2025: Real-world effectiveness of PCV20 against IPD and ACP among older adults in the US

At the 2025 Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global 2025), Ms Amanda Miles, Vaccines Real World Evidence Scientist of Pfizer Vaccines, New York, New York, US, presented the first real-world (RW) data showing the effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) in preventing invasive pneumococcal disease (IPD) and all-cause pneumonia (ACP) among US adults aged ≥65 years.

PCV13 prevents VT IPD and ACP in older adults
Streptococcus pneumoniae is a major cause of community-acquired pneumonia (CAP) and is associated with significant morbidity and mortality among adults. Bacteraemia occurs in about a quarter of pneumococcal pneumonia cases. [PLoS One 2013;8:e60273]

PCV13’s efficacy in pivotal trial
The 13-valent PCV (PCV13) was designed to provide protection against S. pneumoneae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Its approval for use in older adults was based on results of the randomized, placebo-controlled CAPiTA trial (n=84,496) that established its efficacy in preventing vaccine-type (VT) IPD (vaccine efficacy, 75 percent) and nonbacteraemic/noninvasive VT CAP (vaccine efficacy, 45 percent) in adults aged ≥65 years. [N Engl J Med 2015;372:1114-1125] Various post hoc analyses of CAPiTA trial data have further reinforced PCV13’s efficacy in special populations (eg, with underlying comorbidities, age 65–74 and 75–84 years) or by individual serotype (eg, serotype 3, 7F). [Microorganisms 2022;10:127]

Effectiveness against VT IPD
Three observational studies reported PCV13’s vaccine effectiveness estimates against IPD in older adults. Among a cohort of Kaiser Permanente Northern California (KPNC) members aged ≥65 years, PCV13 demonstrated a vaccine effectiveness of 68 percent against VT IPD during the first 4 years of its implementation. [Open Forum Infect Dis 2019;6:S953-S954] Two case-control studies using Active Bacterial Core (ABC) surveillance data, but with different controls groups, found varying vaccine effectiveness estimates against PCV13 VT + 6C IPD. One study using ReferenceUSAGov database controls reported a vaccine effectiveness of 59 percent, while another using Medicare beneficiaries as controls reported a vaccine effectiveness of 47 percent. [Pathogens 2023;12:732]

Effectiveness against ACP
In post hoc analyses of the CAPiTA trial, PCV13 demonstrated a vaccine efficacy of 8.1 percent against ACP in secondary care settings, and 7.4 percent in combined primary and secondary care settings. [Vaccine 2019;37:5777-5787; Microorganisms 2022;10:127; Expert Rev Vaccines 2021;20:269-280]

Three database studies in the US have also reported PCV13’s effectiveness against ACP among older adults. In a cohort of 42,700 adults aged ≥65 years who were enrolled in Kaiser Permanente Southern California (KPSC) health plans, the estimated vaccine effectiveness against ACP was 8.8 percent. [Clin Infect Dis 2022;75:832-841] Another study among 24,121,625 US Medicare beneficiaries ≥65 years of age reported an estimated vaccine effectiveness of 6.7 percent against ACP in hospitalized patients. [JAMA Intern Med 2023;183:40-47] A retrospective cohort study that evaluated 192,061 adults aged ≥65 years within KPNC reported an adjusted vaccine effectiveness of 10 percent against hospitalized ACP. [JAMA Netw Open 2022;5:e221111]

IPD case coverage by PCV20 serotypes
PCV20 expands pneumococcal disease protection beyond PCV13 by including seven additional serotypes (ie, 8, 10A, 11A, 12F, 15B, 22F, and 33F). The US FDA licensed PCV20 in 2021 for prevention of IPD and pneumococcal pneumonia in adults ≥18 years of age based on immunologic noninferiority to existing pneumococcal vaccines. Subsequently, the Advisory Committee on Immunization Practices (ACIP) recommended PCV20 for adults aged ≥65 years. In 2018–2022, 54 percent of IPD cases in adults aged ≥65 years in the US were caused by serotypes included in PCV20. [Microorganisms 2022;10:127; https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2021-biological-license-application-approvals; Hum Vaccin Immunother 2025;21:2469424]

PCV20 RW effectiveness study
A retrospective time-segment cohort study was undertaken to assess the RW effectiveness of PCV20 among older adults in the US. The study’s objectives were: 1) to evaluate PCV20’s effectiveness against all IPD (VT and non-VT) and ACP, and 2) to evaluate the absolute difference in incidence of all IPD and ACP by PCV20 vaccination status. [Miles AC, et al, ESCMID Global 2025, abstract L0003]

Individuals ≥65 years of age were followed through the Medicare health insurance database from July 2022 onwards for first episode of any-serotype IPD and ACP based on ICD-10-CM coding (confirmation of pneumococcal serotype was not available). The study compared PCV20-unvaccinated to PCV20-vaccinated individuals, excluding persons who received PCV20 or PCV15 before July 2022, or 23-valent pneumococcal polysaccharide vaccine (PPSV23) <2 years earlier, or PCV13 <5 years earlier. The follow-up period was approximately 2 years. Inverse probability weighting was used to balance differences in baseline characteristics between the PCV20-vaccinated and PCV20-unvaccinated cohorts, and to address informative censoring due to changes in vaccination status. [Miles AC, et al, ESCMID Global 2025, abstract L0003]

The statistical analyses included calculations of incidence rates (IRs) per 100,000 person-years (PY) and vaccine-preventable disease incidence (VPDI). VPDI was defined as IRPCV20 unvaccinated – IRPCV20 vaccinated. Vaccine effectiveness was calculated using the Cox proportional hazards model with a time-segment approach.

PCV20 effective against all IPD and ACP
“Approximately 16.5 million individuals were eligible for inclusion in the analysis,” explained Miles. “This breaks down to [an estimated sample size of] about 2 million time-segments for PCV20-vaccinated and 16 million time-segments for PCV20-unvaccinated individuals, for a net 12 percent of participants who received PCV20 during the study period.”

PCV20 demonstrated effectiveness against all IPD and ACP in both the overall population and among those who were PCV13- and PPSV23-naive. In the overall cohort, vaccine effectiveness was 25.6 percent against all IPD and 15.2 percent against ACP. In the PCV13- and PPSV23-naive group, vaccine effectiveness was 25.5 and 17.6 percent, respectively. [Miles AC, ESCMID Global 2025, abstract L0003]

The adjusted IRs per 100,000 PY for all IPD and ACP were lower among PCV20-vaccinated vs PCV20-unvaccinated individuals. (Figure)

“PCV20 vaccination prevented 12.5 episodes of IPD and 262 episodes of ACP per 100,000 PY,” noted Miles. “Although vaccine effectiveness was higher against IPD than ACP, the public health impact is substantial against ACP due to its much higher incidence.”

Summary
PCV20 was effective against all IPD and ACP among a diverse population of US adults aged ≥65 years, including those who were PCV13- and PPSV23-naive. The observed vaccine effectiveness aligns with expectations based on prior studies of PCV13. The public health impact of PCV20 vaccination was substantial, especially against ACP. 

This special report is supported by Pfizer Medical.
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