Journal Article

Immunogenicity and safety of co-administration of sabin-strain-based inactivated poliovirus vaccine, diphtheria-tetanus-acellular pertussis vaccine, and live attenuated hepatitis A vaccine in 18-month-old children: A multicenter randomized controlled non-inferiority trial in China

Liu, Xiaoyu, Zhang, Shaobai, Chang, Shaoying, Guo, Yu, Wang, Hui, Wang, Yinan, Chen, Xiao, Chen, Haiping, Zhang, Dan, Wang, Ruize, Shi, Xuanwen, Sun, Li, Zhang, Chao, Hu, Weijun, Han, Shasha

2025

Overview

Frequent healthcare visits increase children's risk of cross-infection. In both routine and emergency settings settings, co-administering vaccines or using combination vaccines can improve coverage, compliance, and timeliness. Vaccination is among the most cost-effective public health measures, with high coverage being critical for success, minimal immune interference, and improved programmatic efficiency. This multicenter, randomized, open-label, non-inferiority phase IV trial extended a prior study (NCT04053010) to evaluate the immunogenicity and safety of co-administering sIPV, DTaP, and HepA-L in healthy Chinese children aged 18 months. Among 600 planned participants, 593 were enrolled and randomized (1:1:1:1) between November 2020 and January 2021: Group 1 (n = 148) received sIPV, DTaP, and HepA-L concomitantly; Groups 2/3/4 (n = 148/148/149) received sIPV, DTaP, or HepA-L separately as comparator controls. Immunogenicity non-inferiority was assessed via adjusted geometric mean ratios (co-ad group vs. sep-ad group per antigen) for poliovirus types I/II/III, DTaP components (DT, TT, PT, FHA), and HepA-L, with a prespecified margin of 0.67 for the 95 % CI lower bound. Antibody titers were assessed at baseline and 30 days post-vaccination: Poliovirus neutralizing antibodies (CPE method; reciprocal ND50 titer), DTaP antibodies (ELISA; IU/mL), HepA-L IgG (electrochemiluminescence immunoassay; IU/L). Safety was monitored for 6 months after vaccination to record any adverse events or serious adverse events. Co-administration demonstrated non-inferior immunogenicity compared to separate administration for all antigens: polio types I (1271.21 vs. 1255.79), II (1915.91 vs. 2076.62), III (2306.41 vs. 2416.62); diphtheria (3.52 vs 3.31 IU/mL), pertussis toxoid (53.87 vs. 64.11 IU/mL); filamentous hemagglutinin (36.02 vs. 35.73 IU/mL), tetanus (9.23 vs 9.08 IU/mL), and hepatitis A (513.24 vs. 439.25 IU/L). Adverse event rates were comparable. Within 30 days post-vaccination, the overall adverse reaction (AR) incidence was higher in the co-administration group (11.49 %) than in Group 4 (4.70 %; P = 0.032) but was comparable to that in Group 2 (9.46 %) and Group 3 (6.08 %). Solicited local reactions occurred at similar rates across groups, with induration and redness being the most frequent. Similarly, fever was the predominant systemic reaction. Most ARs were Grade 1–2 in severity; Grade 3 events were rare (≤1.35 % across groups). No vaccine-related serious adverse events were reported. Simultaneous sIPV+DTaP+HepA-L administration is immunologically non-inferior and exhibits an acceptable safety profile, supporting its potential integration to optimize immunization programs. https://clinicaltrials.gov/study/NCT04636827?cond=NCT04636827&rank=1-ID:NCT04636827. •First RCT study of sIPV+DTaP+HepA-L co-administration in China.•Non-inferior immunogenicity and acceptable safety of combined vaccination.•Reduce healthcare burdens in resource-limited settings.•Facilitates simultaneous childhood vaccination to enhance coverage.•Provides evidence for optimizing pediatric vaccine schedules.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adverse events / Allergies / Allergy and Immunology / Antibodies / Antibodies, Bacterial - blood / Antibodies, Viral - blood / Antigens / Biological products / Children / China / Co-administration / Cross-infection / Diphtheria / Diphtheria-tetanus-acellular pertussis vaccine / Diphtheria-Tetanus-acellular Pertussis Vaccines - administration & dosage / Diphtheria-Tetanus-acellular Pertussis Vaccines - adverse effects / Diphtheria-Tetanus-acellular Pertussis Vaccines - immunology / Electrochemiluminescence / Enzyme-linked immunosorbent assay / Female / Guardians / Health care / Hemagglutinins / Hepatitis / Hepatitis A / Hepatitis A Vaccines - administration & dosage / Hepatitis A Vaccines - adverse effects / Hepatitis A Vaccines - immunology / Humans / Immunization / Immunoassay / Immunogenicity / Immunogenicity, Vaccine / Immunoglobulin G / Inactivated poliovirus vaccine / Infant / Live attenuated hepatitis A vaccine / Lower bounds / Male / Pertussis / Poliovirus Vaccine, Inactivated - administration & dosage / Poliovirus Vaccine, Inactivated - adverse effects / Poliovirus Vaccine, Inactivated - immunology / Public health / Safety / Tetanus / Vaccination - methods / Vaccines / Vaccines, Attenuated - administration & dosage / Vaccines, Attenuated - adverse effects / Vaccines, Attenuated - immunology / Vaccines, Combined - administration & dosage / Vaccines, Combined - immunology / Whooping cough