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.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Simultaneous sIPV+DTaP+HepA-L administration is immunologically non-inferior and exhibits an acceptable safety profile, supporting its potential integration to optimize immunization programs.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04636827?cond=NCT04636827&rank=1-ID:NCT04636827.