What are the expanded recommendations for pneumococcal conjugate vaccine use in adults?

Background
Pneumococcal disease, caused by Streptococcus pneumoniae, remains a significant public health concern, particularly for older adults and those with underlying health conditions.1 This pathogen can lead to invasive diseases such as pneumonia, meningitis, and bacteremia, with increased morbidity and mortality among high-risk populations. Traditionally, pneumococcal vaccination efforts have focused on adults aged 65 years and older. However, recent updates from the Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP) mark a pivotal shift in policy: lowering the age threshold for routine pneumococcal vaccination to include all adults aged 50 and above.2,3

Expanded Recommendation
As of October 23, 2024, ACIP recommends that all pneumococcal conjugate vaccine (PCV) -naïve adults aged ≥50 years receive a single dose of a PCV.2-4 This includes PCV15 (VAXNEUVANCE), PCV20 (Prevnar 20), or the newly approved PCV21 (CAPVAXIVE).3,4 If PCV15 is used, it should be followed by a dose of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) at least one year later, or after 8 weeks in immunocompromised individuals or those who have a cochlear implant or cerebrospinal fluid leak.4

This recommendation represents a major departure from prior guidelines that limited routine vaccination to those aged 65 and older or to individuals aged 19–64 with specific risk conditions.3 The age-based recommendation for those aged 50–64 aims to improve vaccine coverage, simplify clinical decision-making, and address racial and ethnic disparities in pneumococcal disease incidence.

In many parts of the U.S., PCV21 is expected to offer protection against a wider range of pneumococcal strains compared to other available vaccines.3 However, in communities where serotype 4 accounts for 30% or more of pneumococcal disease cases, vaccines that include this serotype, such as PCV20 alone or PCV15 given with PPSV23, may offer more comprehensive coverage against strains circulating locally. For adults aged 19 and older who previously received PCV13 but haven’t yet completed their pneumococcal vaccine series, PPSV23 is no longer recommended to finish the schedule. Instead, completing the series with either PCV20 or PCV21 is advised, in line with current guidelines.

Rationale for the Change
Recent data underscore the substantial disease burden among adults aged 50–64.3 In 2022, this age group experienced invasive pneumococcal disease (IPD) at a rate of 13.2 per 100,000 population and a mortality rate of 1.8 per 100,000; these are rates that approach those observed in the ≥65 years old population (which were 17.2 and 2.7 per 100,000 population, respectively). Notably, approximately 90% of IPD cases in this age group occur in individuals with at least one risk condition such as diabetes, chronic heart or lung disease, or immunosuppression.

The updated guidance also responds to ongoing disparities in disease burden and vaccination rates.3 For instance, IPD incidence peaks at a younger age in Black adults compared to other groups, and pneumococcal vaccination rates are notably lower among racial and ethnic minorities in the 50–64 age bracket.

Clinical trials have demonstrated that PCV15, PCV20, and PCV21 are immunogenic and safe for use in adults aged ≥50.3 The PCV21 vaccine, which covers more serotypes than its predecessors, was also found to elicit statistically superior immune responses for 10 of its 11 unique serotypes compared to PCV20. Safety profiles across all 3 vaccines are favorable, with no major safety signals except a low incidence of Guillain-Barré Syndrome (0.7 cases per million doses) following PCV20 administration.

Economic Outcome Estimations Based on the Change
A recent study by Yi and colleagues evaluated the health and economic outcomes of pneumococcal vaccination strategies for adults aged 50–64 in the U.S.5 Using a Markov model, the researchers compared age-based use of either PCV21 or PCV20 compared to the earlier risk-based recommendation for PCV20 in U.S. adults. Their analysis, conducted from a societal perspective over a lifetime horizon, found clear advantages to using PCV21 in this population.

The study showed that the PCV21 age-based strategy prevented far more cases of pneumococcal disease and related deaths compared to the alternatives; it also proved to be more cost-effective.5 The incremental cost-effectiveness ratio (ICER) for PCV21 was \$73,000 per QALY gained, which was considerably lower than the \$820,000 per QALY observed for the PCV20 age-based strategy. Additional analyses confirmed these results under a range of different assumptions. Even when adjusting for factors like vaccine effectiveness, coverage rates, and fatality risks, PCV21 remained the more efficient option, with ICERs ranging from cost-saving to \$80,000 per QALY gained.

One of the main reasons for PCV21’s stronger performance was its broader serotype coverage which protected against 86.5% of invasive pneumococcal disease cases in this age group, compared to 59.1% for PCV20.5 Importantly, the vaccine remained cost-effective even when the benefits of pediatric vaccination were excluded from the model. Altogether, these findings support the updated ACIP recommendation to routinely offer PCV21 to all adults 50 and older. PCV21 offers a clearer path to reducing disease burden in this population and represents a more efficient use of public health resources.

Conclusion
The new CDC and ACIP recommendation to vaccinate all adults aged ≥50 years against pneumococcal disease marks a critical advancement in adult immunization strategy. By broadening eligibility and simplifying clinical practice, this policy has the potential to reduce disease burden and improve health equity in the United States. It also offers an opportunity to close long-standing gaps in vaccine equity and access. Moving forward, the CDC and ACIP will continue to monitor vaccine safety, effectiveness, and disease trends, including the potential need for booster doses.

References

  1. Centers for Disease Control and Prevention (CDC). Clinical overview of pneumococcal disease. CDC. Updated February 6, 2024. Accessed May 20, 2025. https://www.cdc.gov/pneumococcal/hcp/clinical-overview/index.html
  2. Centers for Disease Control and Prevention (CDC). CDC recommends lowering the age for pneumococcal vaccination from 65 to 50 years old. Updated October 23, 2024. Accessed May 19, 2025. https://www.cdc.gov/media/releases/2024/s1023-pneumococcal-vaccination.html
  3. Kobayashi M, Leidner AJ, Gierke R, et al. Expanded recommendations for use of pneumococcal conjugate vaccines among adults aged ≥50 years: Recommendations of the advisory committee on immunization practices — United States, 2024. MMWR Morb Mortal Wkly Rep 2025;74:1–8. doi: http://dx.doi.org/10.15585/mmwr.mm7401a1
  4. Centers for Disease Control and Prevention (CDC). Pneumococcal vaccine recommendations. Updated October 26, 2024. Accessed May 19, 2025. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html
  5. Yi Z, Owusu-Edusei K, Elbasha EH. Economic evaluation of PCV21 in PCV-naïve adults aged 50-64 years in the United States. Vaccine. Published online May 23, 2025. doi:10.1016/j.vaccine.2025.127264

Prepared by:
Faria Munir, PharmD, MS, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

The information presented is current as of May 27, 2025. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.