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

Abstract 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 study, we descriptively compared 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 IgGs against 14 vaccine serotypes plus cross-protective 6A 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 (seroconversion 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, medically attended, and serious adverse events (SAEs) were captured throughout. Results Between May 2023 to July 2024, 400 participants were enrolled of which 380 (95%) completed the study. Post primary seroconversion rates in the BE-PCV14 arm for common serotypes ranged from 72.6% (serotype 3) to 100% (14, 19F); PCV13 rates ranged from 71.6% to 100% (3 to 14, 19F, 19A). Post booster rates were 87.6–100% for BE-PCV14 and 85.0–100% for PCV13. BE-PCV14 elicited high responses against the two additional serotypes (22F: 96.8%; 33F: 95.3%) and cross-protective 6A (93.0%). Seroconversion rates and Geometric mean concentrations were similar between groups. Most adverse events were mild or moderate; 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, supporting its inclusion in routine infant immunisation programmes. Clinical Trials Registry of India Number: CTRI/2022/11/047366