Co-Administration of PCV13 and PPSV23 Provides Superior Pneumococcal Immunogenicity

A new systematic review and meta-analysis published in the Biological and Pharmaceutical Bulletin shows that sequential covaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) provides superior immunogenicity compared with PPSV23 monotherapy in older adults. The study, which analyzed results from 4 randomized controlled trials involving over 2700 participants, found that this combined approach significantly enhanced bactericidal activity against 11 of the 13 common pneumococcal serotypes evaluated.¹

“No meta-analyses have compared the effectiveness of co-vaccination with PCV13 and PPSV23 (PCV13/PPSV23) vs. PPSV23 monotherapy (PPSV23). Such an analysis is important to better understand the potential benefits of using both vaccines together,” the study authors said. “In countries like Japan, where the PPSV23 vaccine is routinely administered to adults aged ≥65 years through public funding, it plays a significant role in national vaccination programs”

Importantly, this heightened immune response did not come at the cost of patient safety, as the incidence of local and systemic adverse events remained comparable between the 2 vaccination strategies.

For pharmacists on the front lines of public health, understanding these findings is critical as Streptococcus pneumoniae remains a leading cause of community-acquired pneumonia and invasive pneumococcal disease worldwide. This gram-positive bacterium can lead to life-threatening conditions such as meningitis, bacteremic pneumonia, and sepsis, particularly in older adults where the risk of infection increases significantly with age. Although antibiotics such as macrolides and respiratory fluoroquinolones are the mainstay of treatment, the emergence of drug-resistant strains makes prevention through optimized vaccination schedules a primary public health priority.²

The clinical advantage of combining these vaccines lies in their distinct immunological pathways. PCV13 is a conjugate vaccine that induces a T-cell-dependent immune response, which promotes the formation of memory B cells and leads to more robust, long-lasting protection. In contrast, PPSV23 elicits a T-cell-independent response that covers more serotypes but does not generate immunological memory. Furthermore, repeated administration of polysaccharide vaccines can lead to hyporesponsiveness, a phenomenon where the immune response actually diminishes over time.¹

By administering a conjugate vaccine first, the immune system is primed, allowing for a more potent secondary response when the polysaccharide vaccine is subsequently introduced.

Although the meta-analysis focused on the PCV13 and PPSV23 combination, pharmacists must contextualize these findings within the rapidly evolving landscape of modern immunization guidelines. The Centers for Disease Control and Prevention (CDC) now recommends routine vaccination for adults 50 years or older using newer, broader-spectrum conjugate vaccines such as PCV15, PCV20, or PCV21.^3,4

Current CDC guidance often mirrors the sequential logic of the study, specifically recommending that if PCV15 is used, it should be followed by a dose of PPSV23 1 year later to complete the series. However, if the newer PCV20 or PCV21 vaccines are administered, additional doses of PPSV23 are generally not indicated.

Beyond the technical administration of vaccines, pharmacists play a pivotal role in interprofessional teams by educating patients on the benefits of immunization and ensuring compliance with health care recommendations. As the meta-analysis suggests, optimized vaccination strategies can significantly enhance immune protection against the various serotypes of S. pneumoniae, of which over 90 have been identified.^1,2

“These findings suggest that the sequential use of PCV13 followed by PPSV23 may offer enhanced immune protection in older adults and support its use as a potentially more effective vaccination strategy,” the study authors said.¹ “We believe that this meta-analysis has generated strong evidence to support recommendations for the combined use of PPSV23 and PCV-type vaccines in countries that have adopted PPSV23 as their primary vaccination program, as it has demonstrated the efficacy of combining PPSV23 and PCVs.”

By staying abreast of these clinical developments and shifting guidelines, pharmacists can provide evidence-based recommendations that help mitigate the substantial clinical and economic burden of pneumococcal disease in aging populations.

READ MORE: Pneumococcal Resource Center

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REFERENCES

1. Matsumoto Y, Mihara T, Okamoto Y, et al. PCV13/PPSV23 Co-vaccination versus PPSV23 Monotherapy for the Prevention of Pneumococcal Infections: A Systematic Review and Meta-analysis. Biol Pharm Bull. 2026;49(4):666-682. doi:10.1248/bpb.b25-00769

2. Dion CF, Ashurst JV. Streptococcus pneumoniae. [Updated 2025 May 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470537/

3. CDC. Pneumococcal vaccine recommendations. February 25, 2026. Accessed April 13, 2026. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html

4. CDC. Type of pneumococcal vaccines. February 25, 2026. Accessed April 13, 2026. https://www.cdc.gov/pneumococcal/vaccines/types.html