PCV21 Shows Favorable Immunogenicity in Infants, Toddlers Receiving Pediatric Vaccines

In a randomized, modified double-blind, multicenter, active-controlled phase 2 study (NCT04398706), infants who had previously received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13; Pfizer) and unvaccinated toddlers demonstrated favorable immunogenicity towards the 21-valent pneumococcal conjugate vaccine (PCV21; Capvaxive; Merck) when administered concomitantly with routine pediatric vaccines, according to results published in The Pediatric Infectious Disease Journal.^1,2

Pediatrics can receive a pneumococcal conjugate vaccine. | Image Credit: © AbsoluteAI - stock.adobe.com

Pediatrics Carry Unique Risk of Pneumococcal Disease

Pneumococcal disease, caused by infection with Streptococcus pneumoniae (S pneumoniae), presents as a major health threat for young children. The threat of invasive pneumococcal disease (IPD), though not as common as noninvasive disease, is significant given the possibly major complications. Accordingly, there is a high mortality burden for children aged 5 years or less; although the incidence of IPD has declined since the late 1990s, there were still an estimated 294,000 global deaths due to IPD in this population as recently as 2015.^1,3,4

Fortunately, pneumococcal vaccines—especially PCV13, which was introduced in 2009 and widely used in children aged 5 years or less—have lessened the burden of IPD. Newer vaccines, including the 15-valent pneumococcal conjugate vaccine (PCV15; Vaxneuvance, Merck), the 20-valent pneumococcal conjugate vaccine (PCV20; Prevnar20, Pfizer), and the most recently developed PCV21, have been developed to protect against additional serotypes of S pneumoniae.¹

Importantly, PCV21 was approved—and consequently recommended by the Advisory Committee on Immunization Practices—for individuals aged 19 years and older for whom a PCV is recommended. This means that adults aged 65 years and older and individuals aged 19 to 64 with certain pneumococcal risk conditions are recommended to receive PCV21, while PCV15 or PCV20 are used for pediatric vaccination. Currently, PCV21 is undergoing sustained research regarding the potential for use in pediatric populations. In the current study, the investigators evaluated the safety and immunogenicity of 3 different formulations of PCV21 compared with PCV13, administered concomitantly with routine pediatric vaccines.¹

PCV21 Elicits Comparable Immunogenicity in Pediatrics

The first cohort (cohort 1) enrolled toddlers aged 12 to 15 months across 22 centers in the United States from 2020 to 2021. The second cohort (cohort 2) enrolled infants aged 42 to 89 days and was conducted at 35 centers in the US, Canada, and Honduras between 2021 and 2023. Recruiting infants for cohort 2 was only initiated once 70% of participants in cohort 1 had been followed up for 30 days postvaccination. The pediatrics were randomly assigned in a 1:1:1:1 ratio to receive 1 of 3 PCV21 formulations or PCV13. Each PCV21 formulation featured the same serotypes and carrier proteins for each but varied in the number of serotypes with increased antigen content.¹

Prior to beginning the immunogenicity assessment, the investigators affirmed that, overall, the 3 formulations of PCV21 were each well-tolerated with acceptable safety profiles compared with PCV13 in both cohorts. For participants in cohorts 1 and 2, there were no unsolicited AEs within 30 minutes following the vaccine dose. Most of the solicited reactions observed were of grade 1 or 2 intensity and resolved within 3 days; however, the proportion of patients receiving at least 1 solicited injection-site reaction at the PCV21 site was numerically higher than in PCV13 patients.¹

For toddlers who were previously vaccinated with PCV13 in cohort 1, all 3 PCV21 formulations and PCV13 were found to increase serotype-specific immunoglobulin G antibody concentrations. As for the 3 PCV21 formulations, they each demonstrated immunogenicity comparable to that of PCV13 for most of the shared serotypes. For the 8 serotypes specific to PCV21, robust responses were observed for each of the groups.¹

Moving to cohort 2, following the first 3 vaccine doses, each PCV21 formulation demonstrated comparable immune responses to that of PCV13 for most shared serotypes. One month after the fourth vaccine dose, each PCV21 formulation demonstrated comparable immune responses to that of PCV13 for most shared serotypes, with numerically greater responses for the 8 additional serotypes.¹

Lastly, the authors investigated the immune response to coadministered vaccines. Thirty days postvaccination, these responses were comparable between the PCV21 groups and the PCV13 group for the DTaP5-IPV/Hib vaccine in cohort 1; the DTaP5-IPV/Hib, hepatitis B, and rotavirus vaccines in cohort 2; and the measles, mumps, and rubella and varicella vaccines in cohort 2. Interestingly, geometric mean concentrations for the tetanus toxoid and Hib components of the vaccines tended to be higher in the PCV21 groups.¹

These findings not only support routine pediatric vaccine coadministration with pneumococcal vaccination but also provide a robust base of research for future clinical development of PCV21 for pediatric patients. Future research into PCV21’s capabilities in pediatric patients is continuing in phase 3 trials, and pharmacists should stay aware of ongoing research. In the meantime, they can continue to advocate and counsel patients—especially pediatric patients and their guardians—on the benefits of pneumococcal vaccination.¹

REFERENCES

1. Pichon S, Ullery G, Cousin L, et al. Safety and Immunogenicity of a Pneumococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Toddlers and Infants. Ped Infect Dis Journ. 2025. doi:10.1097/INF.0000000000004913

2. Study of a Pneumococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Toddlers and Infants. ClinicalTrials.gov Identifier: NCT04398706. Last Updated September 8, 2025. Accessed September 9, 2025. https://clinicaltrials.gov/study/NCT04398706

3. Wahl B, O’Brien KL, Greenbaum A, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15. The Lancet Global Health. 2018;6(7):E744-E757. DOI: 10.1016/S2214-109X(18)30247-X

4. Mohanty S, Done N, Liu Q, et al. Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998–2019. Vaccine. 2024;42(11):2758-2769. doi:10.1016/j.vaccine.2024.03.013

5. Kobayashi M, Leidner AJ, Gierke R, et al. Use of 21-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024. MMWR Morb Mortal Wkly Rep 2024;73:793–798. doi:10.15585/mmwr.mm7336a3