Pneumococcal Vaccine Failures Among Children Remain Rare

Pneumococcal vaccine failures and breakthrough pneumococcal infections among young childhood patients are reportedly rare, according to a study in Vaccine.¹ However, for the purposes of vaccine efficacy going forward, detailed monitoring of subsequent failures or breakthrough infections will be crucial for the real-world impact of pneumococcal conjugate vaccines (PCVs).

“Globally, Streptococcus pneumoniae is a leading cause of vaccine-preventable morbidity and mortality in infants and children,” according to Vaccines (Basel).² “In recent decades, large-scale pediatric immunization programs have substantially reduced the incidence of invasive pneumococcal disease (IPD). Despite this, residual vaccine-type pneumococcal disease remains in the form of vaccine breakthrough and vaccine failure.”

Belgium’s national analysis of pediatric IPD cases from 2019 to 2024 shows that vaccine failures occurred in only 5.8% of vaccinated children 5 years of age and younger, representing 12.6% of fully vaccinated cases, while breakthrough infections occurred in 8.2%.¹

The failures primarily involved serotypes 19A, 3, and 14, and were significantly associated with older age and clinical presentations of invasive pneumonia.

READ MORE: Capvaxive Receives Additional Indication for High-Risk Children 2 to 17

Under Belgium’s established 2+1 schedule (administered at 2, 4, and 12 months of age), national vaccination coverage has consistently hovered around 94%, helping to suppress circulating vaccine serotypes through herd immunity even among unvaccinated cohorts.¹

These clinical associations mirror previous findings from Catalonia, Spain, where a prospective pediatric study from 2012 to 2016 documented 24 vaccine failure cases. The Spanish researchers noted a tight correlation between vaccine failure and complicated pneumonia, with empyema presenting as the most common complication.³

Crucially, the majority of these cases were diagnosed strictly via polymerase chain reaction (PCR). Traditional culture-based methods often yield negative results due to prior antibiotic treatment in pediatric cohorts, making real-time PCR a critical diagnostic advancement to avoid underdetecting serotypes like serotype 3.^2,3

This cohort, much like the Belgian one, consisted of children without underlying risk factors, suggesting that the failures were vaccine-related rather than host-related, particularly given the lower immunogenicity and antibody response historically observed against serotype 3.³

The clinical picture is further clarified by long-term data from the US. Active Bacterial Core surveillance spanning 2001 to 2016 confirmed that breakthrough infections are exceedingly rare on a population level. Although children on a 2-dose primary series without a booster (the 2+0 schedule) faced significantly higher breakthrough rates in the first year of life compared with a 3-dose primary series (the 3+0 schedule), these differences largely evaporated after 12 months of age or as overall herd immunity matured.⁴

US breakthrough cases were heavily concentrated in serotypes 19A and 3, prompting ongoing evaluations of childhood dosing schedules. Pharmacists look to the Advisory Committee on Immunization Practices (ACIP) for these pediatric recommendations, which are published in the Morbidity and Mortality Weekly Report (MMWR) and serve as the official policy framework.^4,5

As a separate narrative review explains, the persistent threat of serotypes 3 and 19A is directly linked with their high serotype-specific correlates of protection. Despite the general WHO threshold for vaccine licensure being 0.35 micrograms per milliliter of IgG antibody, serotype 19A requires 1.00 micrograms per milliliter, and serotype 3 requires a massive 2.83 micrograms per milliliter to prevent invasive disease.²

The study also notes that although healthy children can experience these rare failures, individuals with underlying comorbidities are at a substantially higher risk of vaccine failure and severe clinical outcomes.

This underscores the necessity of complete series adherence, especially since pediatric series completion rates in developed nations often fall between 79% and 82%, leaving a substantial portion of the population only partially vaccinated and vulnerable to breakthrough infections.²

For pharmacists, who play an increasingly prominent role in immunization delivery, preventing vaccine administration errors is critical to safeguarding pediatric patients. Scheduling errors, such as administering doses too close together, can severely compromise a child’s immunological protection and lead to vaccine failure.⁶

Pharmacists can prevent these failures by implementing robust clinical safeguards, such as isolating look-alike pediatric and adult formulations in storage units, avoiding sequential listings of similarly named vaccines on medical screens, and strictly referencing official ACIP vaccine abbreviations.

As the vaccine landscape shifts toward newer, higher-valent formulations like PCV20, maintaining this high standard of administrative precision and supporting continuous surveillance will be vital to keeping pediatric vaccine failures a rare clinical exception.^1,6

“Vaccine failures and breakthrough infections in young children after PCV10 and PCV13 vaccination in Belgium are rare (5.6% and 8.2% of all vaccinated IPD cases, respectively) and limited to serotypes 19A, 3, 14, and 19F,” concluded authors of the current study.¹ “Ongoing monitoring of vaccine failures post-PCV20 implementation will be crucial to evaluate its real-world impact, identify any gaps in effectiveness, and support evidence-based policy decisions to ensure optimal protection against severe IPD.”

READ MORE: Pneumococcal Resource Center

REFERENCES

1. Dambre C, Cornelissen L, Cuypers L, et al. Pneumococcal vaccines: a dose of change. Vaccine failures and breakthrough infections in Belgian children during the PCV13 era (2019–2024). Vaccine. 2025;72:128065. doi:10.1016/j.vaccine.2025.128065

2. Feemster K, Weaver J, Buchwald U, et al. Pneumococcal vaccine breakthrough and failure in infants and children: a narrative review. Vaccines (Basel). 2023 Nov 24;11(12):1750. doi: 10.3390/vaccines11121750

3. Hernández S, Moraga-Llop F, Díaz A, et al. Failures of 13-valent conjugated pneumococcal vaccine in age-appropriately vaccinated children 2-59 months of age, Spain. Emerg Infect Dis. 2020 Jun;26(6):1147-1155. doi: 10.3201/eid2606.190951

4. Adebanjo TA, Pondo T, Yankey D, et al. Pneumococcal conjugate vaccine breakthrough infections: 2001-2016. Pediatrics. 2020 Mar;145(3):e20190836. doi: 10.1542/peds.2019-0836

5. ACIP recommendations: pneumococcal vaccine. CDC. January 8, 2025. Accessed August 6, 2026. https://www.cdc.gov/acip-recs/hcp/vaccine-specific/pneumococcal.html

6. Vaccine administration: preventing vaccine administration errors. CDC. June 23, 2025. Accessed August 6, 2026. https://www.cdc.gov/vaccines/hcp/admin/downloads/vaccine-administration-preventing-errors.pdf