Standard Pneumococcal Vaccine Schedules Are Suboptimal for High-Risk Children

Among high-risk childhood patients, standard schedules for the pneumococcal conjugate vaccine (PCV) have potential to be suboptimal, according to a study in Human Vaccines & Immunotherapeutics.¹ Since PCVs significantly reduce childhood mortality, yet pneumococcus remains a leading cause of pneumonia mortality, researchers believe a more targeted approach is necessary for this high-risk population.

“The number of patients at high risk requiring protection against invasive pneumococcal disease (IPD) is persistently increasing, owing to increasing numbers of people with underlying medical conditions,” wrote the authors of a study in Vaccines.² “Pneumococcal infection is often more severe in such high-risk individuals than in immunocompetent subjects. Currently, recorded resistance to common antimicrobials further impedes the successful treatment of pneumococcal infections; therefore, optimal protection of high-risk groups against pneumococcal disease, especially children, through vaccination remains challenging.”

For pharmacists managing pediatric immunizations, the challenge lies in the specific timing and biological response of vulnerable populations. Children suffering from severe acute malnutrition, for instance, experience significant lymphoid organ atrophy and impaired innate immunity, which may prevent them from mounting a robust response to standard vaccine doses.¹

Furthermore, the risk of severe pneumonia remains elevated for several months during nutritional recovery, a window of vulnerability that standard 3+0 or 2+1 infant schedules may not adequately cover. Similarly, measles infection can induce immune amnesia, depleting a child’s preexisting antibody repertoire and leaving them susceptible to secondary pneumococcal infections for up to a year following recovery.

READ MORE: Pneumococcal Disease is Rebounding, Requiring Broader Vaccine Distribution

Malaria exposure also complicates the landscape, as parasite-induced inflammation can interfere with the development of effective B-cell memory, potentially limiting the durability of PCV-induced protection.¹

Deciphering the Current PCV Landscape

Clinical guidance increasingly emphasizes that a one-size-fits-all approach is ineffective for children with predisposing conditions such as sickle cell disease, HIV, or chronic organ disease. Although the CDC currently recommends PCV15 or PCV20 for all children under 5 years, those in high-risk categories often require additional doses of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) after the age of 2 to broaden serotype coverage.^2,3

However, pharmacists must be wary of the hyporesponsiveness phenomenon associated with PPSV23, where repeated administration can attenuate the immune response or even erode the immunological memory established by previous PCVs.²

The evolution of vaccine technology, according to Frontiers in Immunology, has led to the recent introduction of PCV20, which adds 7 serotypes to the PCV13 framework to address the rise of nonvaccine serotypes like 8, 10A, and 12F. PCV20 shows strong immunogenicity in the 3+1 regimen. However, its effectiveness in reduced-dose schedules, such as the 1+1 schedule currently utilized in the UK, remains a point of concern for regulatory bodies like the FDA.⁴

What Pharmacists Need to Know for High-Risk Childhood Populations

Pharmacists should note that even with these higher-valency vaccines, certain serotypes remain persistently difficult to neutralize. Serotype 3, in particular, continues to be a major driver of IPD because it releases vast quantities of capsule that can overwhelm vaccine-induced antibodies, as stated by the authors of a study in the Glycoconjugate Journal.⁵

Looking toward the future, the pharmaceutical pipeline is moving toward even broader coverage. Pfizer recently announced positive phase 2 results for a 25-valent PCV, which utilizes next-generation technology to specifically enhance the immune response against serotype 3 by nearly 15-fold compared with current standards.⁶

Other candidates, such as PCV31 and the 24-valent VAX-24, aim to further reduce the “replacement phenomenon” by targeting nearly 94% of disease-causing serotypes.^4,5

For now, the consensus among researchers is that hospital-based catch-up strategies and booster doses timed to periods of recovery from acute illness are essential to closing the immunity gaps that standard schedules leave open for the world’s most vulnerable childhood populations.¹

“Standard PCV schedules may provide suboptimal protection for high-risk groups of children, who are also less likely to benefit from indirect effects in settings with uneven coverage and sustained transmission,” concluded the authors of the current study. “In addition to improving timeliness and completeness of routine PCV and strengthening catch-up delivery to reduce zero-dose and under-vaccinated children, targeted strategies in clearly defined high-risk children to reduce immunity gaps represent important opportunities to reduce inequities and accelerate further declines in pneumococcal disease and mortality.”

READ MORE: Pneumococcal Resource Center

REFERENCES

1. 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.

2. Lagousi T, Papadatou I, Strempas P, et al. Pneumococcal immunization strategies for high-risk pediatric populations worldwide: one size does not fit all. Vaccines (Basel). 2021 Nov 24;9(12):1390. doi: 10.3390/vaccines9121390.

3. Recommended vaccines for children. CDC. February 25, 2026. https://www.cdc.gov/pneumococcal/vaccines/children.html

4. Principi N, Argentiero A, Campana B, et al. PCV20 in pediatric pneumococcal prevention: expanded coverage, remaining challenges. Front Immunol. 2026 Jan 6;16:1707345. doi: 10.3389/fimmu.2025.1707345.

5. 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.

6. Pfizer advances pivotal pediatric pneumococcal vaccine program following strong positive phase 2 results. News Release. Pfizer, Inc. May 20, 2026. Accessed June 9, 2026. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-advances-pivotal-pediatric-pneumococcal-vaccine