PCV21 shows promise as alternative to PCV13 for infants

Three formulations of the 21-valent pneumococcal conjugate vaccine (PCV21) have shown favourable immunogenicity and acceptable tolerability profile among toddlers and infants, when compared with PCV13, in a phase II study. 

“This study supports the evaluation of the PCV21 formulation that had the highest antigen content for selected serotypes for phase III assessment,” the investigators said. 

Toddlers and infants previously vaccinated with three doses of PCV13 (cohort 1; n=140) and unvaccinated infants (cohort 2; n=712) were enrolled in this randomized, double-blind, multicentre, active-controlled phase II trial. Participants were randomly allocated to one of three PCV21 formulations or PCV13, administered at aged 12–15 months (cohort 1) and 2, 4, 6, and 12–15 months (cohort 2). 

The investigators assessed safety throughout the study and immunogenicity 30 days after dose 1 (cohort 1) or doses 3 and 4 (cohort 2). 

Compared with PCV13, all formulations of PCV21 demonstrated acceptable safety profiles. PCV21 exhibited a strong immune response for all serotypes based on serotype-specific immunoglobulin G concentrations in both cohorts. [Pediatr Infec Dis J 2025;44:995-1008] 

Immunogenicity for shared serotypes was generally comparable between PCV13 and PCV21, with numerically higher immunogenicity in the PCV21 cohorts than in the PCV13 cohort for the additional serotypes. Notably, the increased antigen content for selected serotypes was potentially associated with greater immunogenicity. 

Most adverse events (AEs) reported were mild or moderate in intensity, and no serious AEs or AEs of special interest related to the vaccines occurred. The safety findings in the current study were consistent with those of PCV15 and PCV20. [Vaccine 2023;41:2456-2465; Pediatr Infect Dis J2024;43:596-603] 

Cohorts 

In the first cohort, all PCV21 formulations yielded an immune response similar to that of PCV13 for the 13 shared serotypes in toddlers who had received three doses of PCV13 prior to the study. However, only the PCV21 formulations showed a robust antibody response to the eight additionalserotypes. 

"These results suggest that PCV21 could be used in place of PCV13 following initial vaccination with PCV13 in infancy,” the investigators said. 

In the second cohort, PCV21 exhibited immunogenicity following doses 3 and 4. This immunogenicity was also similar to that of PCV13 for most of the shared serotypes but, as expected, was higher for the eight additional serotypes. 

“The increased valency vaccines compared to PCV13, while reaching noninferiority for most of the shared serotypes and maintaining a robust immune response, show a trend for a lower immune response than the reference vaccine (except for serotype 3, for which the PCV21 formulations induced a higher immune response),” according to the investigators.  

“However, the clinical significance for these new generations of PCV vaccines is unclear and, it is anticipated, based on the PCV13 experience, that protection against the disease caused by these vaccine serotypes is maintained,” they added. [Clin Infect Dis 2022;74:1639-1649] 

The development of PCV21 led to a broader coverage against Streptococcus pneumoniae serotypes. It consists of 13 serotypes common to a licensed PCV13 and eight additional serotypes, according to the investigators.