Preclinical Immunogenicity Evaluation of a DTacP-sIPV/Hib Combination Vaccine in Rodent Models Under Varying Formulations and Immunization Schedules

DTacP-sIPV/Hib联合疫苗在不同制剂和免疫程序下于啮齿动物模型中的临床前免疫原性评价

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Abstract

BACKGROUND: Combination vaccines protecting against diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b reduce injection burden and improve compliance. While widely used globally, no domestically produced pentavalent vaccine is currently licensed in China. Recent updates to China's immunization schedule-including earlier initiation and an added booster for pertussis-highlight the need for compatible combination vaccines. This study evaluated the immunogenicity and feasibility of a novel DTacP-sIPV/Hib candidate vaccine in preclinical models. METHODS: The vaccine was assessed in NIH mice and Wistar rats. Two Hib dosages were tested in mice alongside a DTacP-wIPV/Hib vaccine (Pentaxim(®)). In rats, two sIPV formulations (Formulations A and B) were administered using different intervals (1-month vs. 2-month) and injection methods (mixed vs. separate). Antibody titers were measured by ELISA and poliovirus neutralization assays. RESULTS: The candidate vaccine elicited robust immune responses in both models. In mice, after three doses, the high-dose Hib group achieved >90% seroconversion for pertactin antigen, whereas the low-dose group reached 100% for all antigens. In rats, antibody responses after three doses were comparable to those induced by Pentaxim(®), with no significant differences between immunization schedules or administration routes. Compared with Formulation A (containing a higher type I sIPV antigen content), Formulation B exhibited reduced type I poliovirus neutralization after the first dose (p < 0.05) and delayed seroconversion, while responses to other antigens remained similar. CONCLUSION: The candidate DTacP-sIPV/Hib vaccine showed robust immunogenicity and flexibility across schedules and administration methods. A formulation including DT 12.5 Lf, TT 3.5 Lf, PT 25 μg, FHA 25 μg, PRN 8 μg, PRP 10 μg, and sIPV I/II/III at 30/32/45 DU is proposed for further development.

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