Data Suggest Resurgence of Pneumococcal Serotype Despite Vaccination

The unexpected resurgence of Streptococcus pneumoniae serotype 19F is presenting a significant challenge to public health, even as pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) reach their 25th anniversary. Although these vaccines have historically succeeded in nearly eliminating many targeted serotypes, recent data suggests that 19F is staging a comeback, particularly among older populations.¹

“This phenomenon of resurgence of vaccine-targeted serotypes is not well understood,” the study authors said. “Understanding the mechanism driving these patterns is critical to determine whether additional serotypes might resurge in the future and how such increases could be prevented.”

In the United States, the frequency of adult invasive pneumococcal disease (IPD) cases caused by 19F has now reached or exceeded levels recorded in 1998, prior to the introduction of the first 7-valent vaccine. This phenomenon is particularly striking because 19F is included in all current vaccine formulations, yet it continues to persist and resurge in multiple geographic regions, including Australia and the United Kingdom.^1,2

For pharmacists on the front lines of immunization, understanding the biological hurdles associated with serotype 19F is essential for patient counseling and advocate efforts. Unlike many other serotypes, 19F is uniquely difficult to protect against, requiring higher antibody concentrations to prevent both colonization in the nasopharynx and progression to invasive disease.¹

Furthermore, research indicates that 19F generates weaker memory B cell responses compared to other serotypes, potentially leading to a shorter duration of effective protection. This biological toughness may be related to the thickness or composition of its bacterial capsule, which can make it more resistant to the immune system’s primary defenses.

The resurgence of this serotype is likely driven by a combination of factors, including shifts in vaccination strategy and ecological competition. One leading hypothesis suggests that as higher-valency vaccines like 13-valent pneumococcal conjugate vaccine (PCV13), PCV15, and PCV20 eliminate more serotypes, they reduce competition in the nasopharynx, which allows serotype 19F to expand. Additionally, the timing of serotype 19F increase in the US coincided with changes in adult vaccination policies, including the transition to a sequential schedule of PCV13 followed by the 23-valent polysaccharide vaccine (PPSV23). Some researchers speculate that certain vaccination strategies or a decline in the natural boosting of immunity through community exposure may have left older adults more susceptible to transmission and disease.

Beyond biological persistence, pharmacists should be aware of emerging genetic variants that complicate the clinical landscape. Evidence from Brazil has uncovered a predominant lineage of 19F variants that can lead to misinterpretation in capsular typing. These variants possess minor modifications in the wzy gene, a common target for PCR-based identification, which can result in false-negative results during surveillance and diagnostics.²

Although many of these variant isolates remain susceptible to most antibiotics, some multidrug-resistant lineages have been reported globally, highlighting the continued need for vigilance regarding antimicrobial resistance in 19F strains.^1,2

The persistence of 19F underscores the critical importance of adhering to recommended vaccination schedules, particularly regarding booster doses. In pediatric populations, infants and young children typically require a 4-dose series at 2, 4, 6, and 12 to 15 months of age to ensure robust protection. Communities with lower uptake of the booster dose have shown slower elimination of vaccine-targeted serotypes, suggesting that pharmacists can play a pivotal role in ensuring children complete the full series. For adults, current recommendations emphasize PCV15 or PCV20 for those 50 years and older, or younger adults with specific risk factors like chronic lung disease or immunocompromising conditions.³

Looking forward, the arrival of next-generation vaccines, including a 21-valent formulation designed specifically for adults, offers hope for addressing the remaining burden of pneumococcal disease. However, the 19F experience serves as a reminder that the population dynamics of S. pneumoniae are highly fluid.

Pharmacists must remain informed about these shifts to provide accurate guidance on the risks of pneumonia, meningitis, and bacteremia, and to help patients navigate the evolving landscape of pneumococcal prevention. High-quality surveillance and a focus on maintaining high vaccination coverage across all age groups remain the most effective tools for mitigating the resurgence of these resilient pathogens.

“There are still many key questions that need to be answered to understand this phenomenon,” the study authors concluded.¹ “Many of these questions can be addressed through high-quality surveillance and analysis of existing data.”

READ MORE: Pneumococcal Resource Center

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REFERENCES

1. Thindwa D, Carcamo PM, Dagan R, Weinberger DM. What is driving the resurgence and persistence of vaccine-targeted pneumococcal serotypes?-Serotype 19F as the paradigm. PLoS Pathog. 2026;22(3):e1014065. Published 2026 Mar 19. doi:10.1371/journal.ppat.1014065

2. Oliveira LMA, Souza ARV, Pinto TCA, Teixeira LM. Characterization of Streptococcus pneumoniae serotype 19F-variants occurring in Brazil uncovers a predominant lineage that can lead to misinterpretation in capsular typing. Int J Infect Dis. 2021;104:580-583. doi:10.1016/j.ijid.2021.01.030

3. CDC. Pneumococcal Conjugate Vaccine: What You Need to Know. May 29, 2025. Accessed March 25, 2026. https://www.cdc.gov/vaccines/hcp/current-vis/downloads/pcv.pdf