Objectives: To determine whether a Sabin strain inactivated poliovirus booster (sIPV) given concomitantly (same day, different sites) with MMRV or inactivated hepatitis A vaccine (HepA) is non-inferior in immunogenicity and comparable in safety to separate administration at the 18-month visit. Methods: Open-label, randomized Phase IV trial in healthy children (18~22 months), allocated 2:2:2:1:1 to sIPV&MMRV, sIPV&HepA, sIPV-only, MMRV-only, or HepA-only. Primary endpoints were Day-30 seroconversion rates (SCRs) for poliovirus types 1–3 (sIPV arms) and for HepA (HepA arms). Results: Of 892 screened, 889 were randomized; baseline characteristics were balanced. By Day 30, seroprotection was 100% for PV types 1–3 in all sIPV-containing arms. SCRs were high and similar across concomitant vs. separate administration; all pairwise SCR differences met non-inferiority (−10% margin). Adjusted post-vaccination GMTs were comparable across serotypes. For HepA, Day-30 SPoR was 99.3% vs. 100.0%, and adjusted GMC was 412.2 vs. 465.9 (p = 0.2224). For MMRV, Day-30 SPoR was 100% in both groups with similar adjusted GMCs. Within 30 days, overall adverse reactions were 14.5%/17.4%/16.3%/7.3%/10.8% (sIPV&MMRV/sIPV&HepA/sIPV-only/MMRV-only/HepA-only), mostly mild to moderate; no vaccine-related SAEs (NCT06442449). Conclusions: Same-day sIPV co-administration with MMRV or HepA was non-inferior and well tolerated, supporting programmatic adoption.

Background: The three commercial Enterovirus 71 (EV71) inactivated vaccines which have effectively controlled the EV71 pandemic currently rely on inherent variable in vivo potency methods for batch release. To align with 3R (Replacement, Reduction, Refinement) principles and enhance quality control, this study referred to WHO guidelines and the European Pharmacopoeia to develop in vitro relative potency (IVRP) methods. Methods: Working standards tracing to phase 3 clinical vaccines were established. Manufacture-specific IVRP methods were developed and validated per ICH Q14/Q2(R2), utilizing conformational epitope-targeting neutralizing monoclonal antibodies (MAbs). One of the MAbs (CT11F9) recognition sites was clarified with Cryo-EM. Subsequently, the performance of IVRP was assessed using varied concentrations and heat-treated vaccines. The correlation between IVRP and in vivo methods was analyzed, followed by setting IVRP specifications. Results: The manufacturer-specific working standard exhibited ED50 values comparable to those of related phase 3 clinical vaccines. All IVRP methods achieved a relative bias/precision/total error ≤ 15%. The IVRP methods correlated with in vivo methods (p < 0.05, r > 0.9) can discriminate EV71 antigen concentrations (p < 0.01, r > 0.99) and indicate the stability of the vaccines. Cryo-EM was adopted to identify the epitopes recognized by CT11F9, revealing that this neutralizing antibody recognizes a conformational epitope spanning VP1-3 of the same protomer. Using 31–47 batches of commercial vaccines, IVRP specifications were proposed as 0.56–1.35, 0.58–1.40, and 0.54–1.50. Conclusions: Based on conformational epitope-targeting neutralizing MAbs, manufacturer-specific IVRP methods, which were sensitive to process variations and correlated with in vivo results, have been established. IVRP methods provide a reliable, animal-free alternative for EV71 vaccine batch release.

Objectives To determine whether a Sabin-strain inactivated poliovirus booster (sIPV) given concomitantly (same day, different sites) with MMRV or inactivated hepatitis A vaccine (HepA) is non-inferior in immunogenicity and comparable in safety to separate administration at the 18-month visit. Methods Open-label, randomized Phase IV trial in healthy children (18 months + 4), allocated 2:2:2:1:1 to sIPV&MMRV, sIPV&HepA, sIPV-only, MMRV-only, or HepA-only. Primary endpoints were Day-30 seroconversion rates (SCRs) for poliovirus types 1–3 (sIPV arms) and for HepA (HepA arms). Results Of 892 screened, 889 were randomized; baseline characteristics were balanced. By Day 30, seroprotection was 100% for PV types 1–3 in all sIPV-containing arms. SCRs were high and similar across concomitant vs separate administration; all pairwise SCR differences met non-inferiority (−10% margin). Adjusted post-vaccination GMTs were comparable across serotypes. For HepA, Day-30 SPoR was 99.3% vs 100.0% and adjusted GMC 412.2 vs 465.9 (P=0.2224). For MMRV, Day-30 SPoR was 100% in both groups with similar adjusted GMCs. Within 30 days, overall adverse reactions were 14.5% / 17.4% / 16.3% / 7.3% / 10.8% (sIPV&MMRV / sIPV&HepA / sIPV-only / MMRV-only / HepA-only), mostly mild–moderate; no vaccine-related SAEs. (NCT06442449) Conclusions Same-day sIPV co-administration with MMRV or HepA was non-inferior and well tolerated, supporting programmatic adoption.

Background: In China, the current national immunisation schedule extends only to 4 years of age, and no polio booster dose is recommended for adolescents or adults, with data on immunogenicity and safety in these populations lacking. This phase IV trial evaluated the immunogenicity and safety of a single booster dose of Sabin-strain inactivated poliovirus vaccine (sIPV) in Chinese adolescents and adults. Methods: This phase IV, open-label trial enrolled 120 healthy participants, comprising 60 adolescents aged 7–17 years and 60 adults aged 18–50 years, who received a single booster dose of sIPV. Participants were enrolled and vaccinated in Gansu Province, China, between 21 October and 1 November 2025. Immunogenicity was assessed by neutralising antibody titres against poliovirus types 1, 2, and 3 before and 30 days post-vaccination. Safety was evaluated through monitoring of adverse events throughout the 30-day follow-up period. Results: Following a single sIPV booster dose, seropositivity rates reached 100% for all three poliovirus serotypes in both age groups. Post-vaccination geometric mean titres (GMTs) for types 1, 2, and 3 were 1748.29, 3961.77, and 2089.08 in adolescents, and 1902.58, 4434.39, and 2256.16 in adults, respectively, with no significant between-group differences. Seroconversion rates for type 3 were significantly higher in adults than in adolescents (98.33% vs. 86.67%, p = 0.032). Geometric mean increases (GMIs) were significantly higher in adults for type 1 (72.12 vs. 28.10, p = 0.008) and type 3 (316.14 vs. 45.56, p < 0.001). The vaccine was well tolerated; vaccine-related adverse events were reported in 17.50% of participants, all mild to moderate, with no vaccine-related serious adverse events. Conclusions: A single booster dose of sIPV induced robust neutralising antibody responses across all three poliovirus serotypes in both adolescents and adults, with a favourable safety profile. Adults with lower baseline immunity derived proportionally greater fold-increases in antibody titres.