Pneumococcal Vaccines Fail to Clearly Protect High-Risk Adults Under 65

Among high-risk adults aged 18 to 64 years old, pneumococcal vaccination exhibited no significant protection against community-acquired pneumonia (CAP) hospitalization, according to a study published in Pneumonia. With the pneumococcal polysaccharide vaccine (PPSV23) likewise showing little-to-no protection, researchers claim further developing pneumococcal conjugate vaccines (PCVs) and optimizing vaccine schedules can reverse these trends.¹

“Pneumococcal vaccine recommendations have changed more than any other vaccine recommendations during my time in practice, which is why it is important for all of us to stay up to date with the latest vaccine recommendations through attending continuing education programs and also by referring to the most recent vaccination schedules from organizations such as the American Academy of Family Physicians, the American Academy of Pediatrics, and the CDC,” Gretchen K. Garofoli, PharmD, BCACP, CTTS, FAPhA, clinical professor at the West Virginia University School of Pharmacy, told Drug Topics®.² “Patients do not need to receive a pneumococcal vaccine annually but based on their age and risk conditions.”

The multicenter case-control study between 2020 and 2024, involving over 1600 participants, revealed that neither PPSV23, PCVs, nor sequential vaccination strategies provided a statistically significant shield against CAP-related hospitalization for this demographic.¹

READ MORE: Standard Pneumococcal Vaccine Schedules Are Suboptimal for High-Risk Children

For immunocompromised individuals, those who received only PPSV23 actually demonstrated a significantly negative adjusted vaccine effectiveness (VE), a finding researchers suggest may stem from a confounding bias by indication, where those at the highest inherent risk of severe outcomes are also the most likely to be prioritized for vaccination.

This is particularly concerning for pharmacists to consider, as Streptococcus pneumoniae remains the most common causative agent in CAP for both immunocompetent and immunocompromised adults, potentially leading to severe complications like meningitis, bacteremia, and kidney-damaging sepsis.^1,3

Although pneumococcal pneumonia accounts for 10% to 30% of adult CAP cases and leads to over 225,000 annual hospitalizations in the US, the inability of current vaccines to clearly protect at-risk younger adults highlights a major gap in the proactive shield pharmacists aim to build for their patients.^1-3

A primary factor in this lack of effectiveness is the biological resilience of specific bacterial strains, most notably serotype 3, which remains a leading cause of invasive disease despite its inclusion in the PCV13 vaccine. Serotype 3 produces profuse quantities of a mucoid capsule that is not covalently attached to the bacterial surface, allowing the constant release of polysaccharides that can overwhelm vaccine-induced antibodies.^4,5

A systematic review of serotype distribution across 18 countries confirmed that serotype 3 is the most prevalent strain causing pneumonia in adults, maintaining a high burden even after decades of vaccination efforts. Furthermore, although older vaccines like PPSV23 cover 23 different serotypes, they fail to generate long-term immunological memory or reduce the carriage of bacteria in the nasopharynx—critical components for achieving herd protection.

For pharmacists navigating this evolving landscape, the choice of vaccine must be increasingly individualized, as the clinical efficacy of these tools depends on a symphony of factors, including the patient's lifestyle, medical history, and geography. For example, despite PCV20 being recommended for adults 18 and older with risk conditions, its coverage of serotype 4 is particularly vital for unhoused populations in the Western US, where that strain is more prevalent.^1,2

This level of precision is necessary because the widespread use of vaccines has led to serotype replacement, a process where nonvaccine strains like 15A, 23A, and 35B fill the ecological niche left by the reduction of vaccine-targeted serotypes. As of October 2024, the CDC has lowered the recommended age for routine pneumococcal vaccination to 50, reflecting how the risk of serious illness increases significantly with age and the presence of underlying conditions like chronic heart or lung disease.^1-5

Lessons from global pediatric strategies suggest that the timing of vaccination may be as critical as the formulation itself, particularly for those with infection-associated immune dysfunction. Research into high-risk children in low- and middle-income countries indicates that vaccination timed to periods of greatest vulnerability may be required to overcome temporary immune amnesia and close persistent gaps in protection.⁶

Until these advancements are widely available, pharmacists must remain the lead conductors of preventative care, staying updated on the latest schedules and prioritizing the use of higher-valency conjugate vaccines to maximize protection for their most vulnerable patients.^1,2,6

“We observed no significant protection of pneumococcal vaccination against hospitalization for CAP in adults aged [below] 65 years with underlying risk factors,” concluded the authors of the current study.¹ “Our results highlight the need to improve VE by prioritizing conjugate vaccine-based strategies and optimizing vaccination schedules tailored to specific risk groups.”

READ MORE: Pneumococcal Resource Center

REFERENCES

1. Liébana M, Toledo D, Soldevila N, et al. A multicentre case-control study about effectiveness of pneumococcal vaccination against pneumonia hospitalization in at-risk adults. Pneumonia (Nathan). 2026 Jun 5;18(1):13. doi: 10.1186/s41479-026-00201-6.

2. Nowosielski B, Garofoli GK. FAQ: how a variety of pneumococcal vaccines protect patient populations. Drug Topics. May 12, 2026. Accessed June 12, 2026. https://www.drugtopics.com/view/how-a-variety-of-pneumococcal-vaccines-protect-patient-populations

3. Weber D. Pneumococcal pneumonia vaccination in adults explained. Pfizer. August 13, 2025. Accessed June 12, 2026. https://www.pfizerforall.com/vaccines/education/what-is-the-pneumococcal-vaccine-for

4. Micoli F, Romano MR, Carboni F, et al. Strengths and weaknesses of pneumococcal conjugate vaccines. Glycoconj J. 2023 Apr;40(2):135-148. doi: 10.1007/s10719-023-10100-3.

5. Mrabt F, Guedes S. Systematic review on serotypes distribution of pneumococcal pneumonia in adults and the elderly. BMC Public Health. 2025 Mar 29;25(1):1194. doi: 10.1186/s12889-025-22164-x.

6. Hart J, Toh ZQ, Do LAH, et al. Targeted pneumococcal conjugate vaccination strategies for high-risk children. Hum Vaccin Immunother. 2026 Dec;22(1):2683209. doi: 10.1080/21645515.2026.2683209.