Immunogenicity and safety of biological E's 14-valent pneumococcal conjugate vaccine (PNEUBEVAX 14®) administered in a 2p + 1 schedule to healthy infants: a multicenter, randomized, active controlled, single-blind, phase III trial.

Background: Pneumococcal conjugate vaccines (PCVs) have markedly reduced childhood pneumococcal diseases, yet serotype replacement and regional heterogeneity remain important challenges. The World Health Organization recommends either a 3p + 0 or 2p + 1 schedule for PCV immunization programmes. BE-PCV14, a 14-valent vaccine, has previously been shown to be non-inferior to PCV13 in a 3p + 0 regimen. In this Phase III trial, we aimed to descriptively compare the immunogenicity and safety of BE-PCV14 and PCV13 in a 2p + 1 schedule in Indian infants. Methods: In this randomized, single-blind, multicenter trial, 400 PCV-naïve infants (6-8 weeks old) were randomized 1:1 to receive either BE-PCV14 or PCV13; at 6 and 14 weeks, with a booster at 9 months. Serum IgG against 14 vaccine serotypes plus cross-protective 6 A were measured at post primary (28 days post dose 2), pre booster (at 9 months) and post booster (30 days post dose 3) time points. The primary endpoint was the proportion achieving IgG ≥0.35 μg/mL (seroresponse rate) for the 12 serotypes common to both vaccines at post primary, pre booster and post booster time points. Solicited local and systemic reactions were recorded for 7 days after each dose; unsolicited, and serious adverse events (SAEs) were captured throughout. Findings: Between May 2023 and July 2024, 400 participants were enrolled of which 380 (95%) completed the study. Post primary seroresponse rates in the BE-PCV14 arm for common serotypes ranged from 72.6% (95% CI: 65.8, 78.5) (serotype 3) to 100% (95% CI: 98.0, 100.0) (14, 19 F); PCV13 rates ranged from 71.6% (95% CI: 64.9, 77.5) to 100% (95% CI: 98.1, 100.0) (14, 19 F, 19 A). Post booster rates were 87.6% (95% CI: 82.1, 91.6) to 100% (95% CI: 98.0, 100.0) for BE-PCV14 and 85.0% (95% CI: 79.4, 89.4) to 100% (95% CI: 98.1, 100.0) for PCV13. BE-PCV14 elicited high responses against the two additional serotypes, i.e., 22 F: 96.8% (95% CI: 93.1, 98.5), 33 F: 92.5% (95% CI: 87.8, 95.5), and cross-protective 6 A: 93.0% (95% CI: 88.4, 95.9). Of the participants that received BE-PCV14 or PCV13, 33.5% (95% CI: 27.3, 40.3) and 38% (95% CI: 31.6, 44.9) had mild AEs and 11.5% (95% CI: 7.8, 16.7) and 10.5% (95% CI: 7.0, 15.5) had moderate AEs, respectively. Two unrelated SAEs occurred in the BE-PCV14 arm. Interpretation: Administered in a 2p + 1 schedule, BE-PCV14 was highly immunogenic, well tolerated, and comparable to PCV13 while broadening serotype coverage. These findings support consideration of BE-PCV14 for routine infant immunization programmes using a 2p + 1 schedule, particularly in settings where the additional serotypes contribute to ongoing pneumococcal disease. Funding: This clinical research was exclusively funded by Biological E. Limited, Hyderabad, India.