FDA Approves Merck’s Pneumococcal 21-Valent Conjugate Vaccine for High-Risk Children and Adolescents Aged 2 Through 17

FDA has approved an expanded indication for Merck’s pneumococcal 21-valent conjugate vaccine (Capvaxive) for the prevention of invasive pneumococcal disease (IPD) in children and adolescents aged 2 through 17 years who have completed a primary pediatric pneumococcal vaccination series and have one or more chronic medical conditions placing them at increased risk for pneumococcal disease. The company announced the approval on June 18, 2026, and stated that the vaccine is now the only pneumococcal conjugate vaccine (PCV) in the United States specifically indicated and studied for use in this population.¹ The approval is supported by immunogenicity and safety data from a phase trial (STRIDE-13).

"Children and adolescents with certain chronic conditions are at an increased risk for pneumococcal disease, including pneumonia, meningitis, and bloodstream infections," said Rotem Lapidot, MD, chief of Pediatric Infectious Diseases at Rambam Health Care Campus and STRIDE-13 investigator. "This approval recognizes the potential of [Capvaxive] to deliver additional protection by including serotypes not contained in approved primary pediatric PCV series."

What did the STRIDE-13 trial show, and how was the approval supported?

STRIDE-13 (NCT06177912) was a randomized, double-blind, active comparator–controlled phase 3 study enrolling 874 individuals aged 2 through 17 years with one or more prespecified chronic conditions, including diabetes mellitus, chronic heart disease, chronic kidney disease, chronic liver disease, and chronic lung disease. These were patients who had completed a primary pneumococcal vaccination regimen at least 8 weeks prior to enrollment. Participants were randomized 3:2 to receive a single dose of pneumococcal 21-valent conjugate vaccine (n=527) or pneumococcal 23-valent polysaccharide vaccine (PPSV23) (n=347). Pneumococcal 21-valent conjugate vaccine was noninferior to PPSV23 for the 12 shared serotypes and induced statistically significantly greater opsonophagocytic activity (OPA) geometric mean titers compared to PPSV23 for the 9 serotypes unique to pneumococcal 21-valent conjugate vaccine.¹

In a post hoc analysis, pneumococcal 21-valent conjugate vaccine was also noninferior to PPSV23 for serotype 15B, reflecting cross-reactive immune responses to serotype 15C. Solicited adverse reactions lasted a median of 2 days, with most resolving within 3 days. Serious adverse events (SAEs) within six months post-vaccination were reported in 5.5% of pneumococcal 21-valent conjugate vaccine recipients and 7.2% of PPSV23 recipients, with no notable patterns between groups. According to the data, 1 pneumococcal 21-valent conjugate vaccine recipient experienced grade 2 syncope that required hospitalization within 3 minutes of vaccination and was considered vaccine-related.¹

How does the vaccine’s composition differ from existing pediatric pneumococcal vaccines?

Pneumococcal 21-valent conjugate vaccine was originally designed and approved for adults, incorporating eight serotypes (15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B) not contained in other currently approved pneumococcal vaccines including PCV15 and PCV20.² This serotype composition is intended to address the residual IPD burden from strains not covered by existing primary pediatric series, rather than replace them.

Merck’s vaccine is administered as a single dose and is positioned as a supplementary vaccine for at-risk children who have already completed a primary series, addressing serotype gaps relevant to adult-pattern IPD that increasingly accounts for cases in medically complex pediatric patients.² The vaccine is approved under accelerated approval for the pneumonia indication based on OPA immune response data. Continued approval for that indication is contingent on verification of clinical benefit in a confirmatory trial.

What is the significance of the immunogenicity-based approval and the available pediatric data?

The STRIDE-13 approval rests on immunogenicity endpoints, OPA geometric mean titers, rather than clinical efficacy outcomes such as confirmed IPD or pneumonia episodes. While OPA responses are accepted surrogates for pneumococcal vaccine efficacy based on established correlates of protection, no clinical endpoint trial in the pediatric at-risk population has been completed.³ The active comparator used, PPSV23, a polysaccharide rather than conjugate vaccine, has known immunological limitations in younger children due to T-cell-independent immune responses, which may favor pneumococcal 21-valent conjugate vaccine's conjugate platform in this age group but may also limit the interpretive value of the non-inferiority comparison.³ The expanded indication applies specifically to the at-risk pediatric population and does not alter the primary immunization schedule for healthy children.

What are the key limitations of this approval, and what further evidence is anticipated?

Vaccine efficacy against confirmed IPD or pneumococcal pneumonia in children and adolescents with chronic medical conditions has not yet been established as the approval is based on immunogenicity surrogates. A confirmatory trial required under accelerated approval for the pneumonia indication has not yet been initiated or registered publicly.

Immunocompromised patients may generate attenuated responses to pneumococcal 21-valent conjugate vaccine, which is an important consideration given that many at-risk pediatric patients receive immunosuppressive therapies.⁴ Long-term persistence of immune responses in this population and optimal timing relative to primary series completion would require further characterization.

References

1. Merck. US FDA approves an additional indication for CAPVAXIVE (pneumococcal 21-valent conjugate vaccine) in children and adolescents aged 2 through 17 at increased risk for pneumococcal disease. Published June 18, 2026. Accessed June 18, 2026. https://www.merck.com/news/u-s-fda-approves-an-additional-indication-for-capvaxive-pneumococcal-21-valent-conjugate-vaccine-in-children-and-adolescents-aged-2-through-17-at-increased-risk-for-pneumococcal-disease/
2. Kobayashi M, Pilishvili T, Farrar JL, et al. Pneumococcal vaccine for adults aged ≥19 years: recommendations of the Advisory Committee on Immunization Practices, United States, 2023. MMWR Recomm Rep. 2023;72(3):1-39. doi:10.15585/mmwr.rr7203a1
3. Tin Tin Htar M, Christopoulou D, Schmitt HJ. Pneumococcal serotype evolution in Western Europe. BMC Infect Dis. 2015;15:419. doi:10.1186/s12879-015-1147-x
4. Musher DM, Anderson R, Feldman C. The remarkable history of pneumococcal vaccination. Pneumonia. 2022;14(1):5. doi:10.1186/s41479-022-00097-y