Merck's investigational 21-valent pneumococcal conjugate vaccine (PCV21, Capvaxive) demonstrated favorable immunogenicity and safety when administered concomitantly with routine pediatric vaccines in a phase 2 study, according to results published in The Pediatric Infectious Disease Journal. The findings represent a significant step toward expanding protection against pneumococcal disease in pediatric populations.
Study Design and Patient Population
The randomized, modified double-blind, multicenter, active-controlled phase 2 study (NCT04398706) enrolled participants across two cohorts. Cohort 1 included toddlers aged 12 to 15 months across 22 centers in the United States from 2020 to 2021, while cohort 2 enrolled infants aged 42 to 89 days at 35 centers in the US, Canada, and Honduras between 2021 and 2023.
Participants were randomly assigned in a 1:1:1:1 ratio to receive one of three PCV21 formulations or the current standard PCV13 (Prevnar 13, Pfizer). Each PCV21 formulation featured the same serotypes and carrier proteins but varied in the number of serotypes with increased antigen content. Cohort 1 participants had previously received three doses of PCV13, while cohort 2 participants were unvaccinated toddlers.
Safety Profile and Tolerability
The investigators confirmed that all three PCV21 formulations were well-tolerated with acceptable safety profiles compared with PCV13 in both cohorts. No unsolicited adverse events occurred within 30 minutes following vaccine administration in either cohort. Most solicited reactions were of grade 1 or 2 intensity and resolved within three days, though the proportion of patients receiving at least one solicited injection-site reaction at the PCV21 site was numerically higher than in PCV13 patients.
Immunogenicity Results
Toddler Cohort Performance
For toddlers previously vaccinated with PCV13 in cohort 1, all three PCV21 formulations and PCV13 increased serotype-specific immunoglobulin G antibody concentrations. The PCV21 formulations demonstrated immunogenicity comparable to PCV13 for most shared serotypes, while showing robust responses for the eight serotypes specific to PCV21.
Infant Cohort Outcomes
In cohort 2, following the first three vaccine doses, each PCV21 formulation demonstrated comparable immune responses to PCV13 for most shared serotypes. One month after the fourth vaccine dose, each PCV21 formulation maintained comparable immune responses to PCV13 for most shared serotypes, with numerically greater responses for the eight additional serotypes.
Concomitant Vaccine Administration
The study evaluated immune responses to coadministered vaccines, finding comparable responses between PCV21 groups and the PCV13 group 30 days post-vaccination. This included DTaP5-IPV/Hib vaccine in cohort 1, and DTaP5-IPV/Hib, hepatitis B, and rotavirus vaccines in cohort 2, as well as measles, mumps, rubella, and varicella vaccines in cohort 2. Notably, geometric mean concentrations for the tetanus toxoid and Hib components tended to be higher in the PCV21 groups.
Clinical Context and Disease Burden
Pneumococcal disease, caused by Streptococcus pneumoniae infection, presents a major health threat for young children. Despite the decline in invasive pneumococcal disease (IPD) incidence since the late 1990s following vaccine introduction, there were still an estimated 294,000 global deaths due to IPD in children aged 5 years or less as of 2015.
Currently, PCV21 is approved and recommended by the Advisory Committee on Immunization Practices for individuals aged 19 years and older for whom a pneumococcal conjugate vaccine is recommended. This includes adults aged 65 years and older and individuals aged 19 to 64 with certain pneumococcal risk conditions, while PCV15 or PCV20 are used for pediatric vaccination.
Future Development
The findings provide a robust foundation for future clinical development of PCV21 in pediatric patients, with phase 3 trials currently ongoing. The results support routine pediatric vaccine coadministration with pneumococcal vaccination and demonstrate the potential for PCV21 to offer broader protection against additional pneumococcal serotypes in the pediatric population.
