Journal Article

Safety, immunogenicity and immune persistence of a lyophilized purified human diploid cells rabies vaccine following rabies PEP regimen Essen and Zagreb: A randomized, blinded controlled phase 3 trial in healthy participants aged 10–60 years old

Liang, Qi, Zhao, Danhua, Xu, Bidan, Cao, Shouchun, Hu, Jialei, Wu, Xiaohong, Li, Guifan, Zhang, Lei, Shi, Leitai, Li, Yixin, Liu, Yafei

2025

Overview

To evaluate the safety, immunogenicity and immune persistence of a lyophilized purified human diploid cells rabies vaccine in healthy and previously unvaccinated people in a simulated rabies post-exposure prophylaxis, by traditional 5-dose Essen regimen and abbreviated 4-dose Zagreb regimen. A cohort of 1800 healthy participants aged 10–60 years old were randomized into three groups: 5-dose test group (T5, Essen regimen), 5-dose control group (C5, Essen regimen) and 4-dose test group (T4, Zagreb regimen) according to the ratio of 1:1:1, and inoculated with trial vaccine or control vaccine separately to analyze the safety of vaccine as well as rabies antibody levels before and after vaccination. Adverse reactions (AEs) mainly occurred after the initial dose of immunization, which were mostly mild (grade 1) in severity. The incidence of total AEs in T4 (38 %) was lower than that in C5 (45 %) (P = 0.02) from the initial dose to 28 days after the final dose; fever rate in T5 (12 %, P = 0.01) and T4 (13 %, P = 0.03) was lower than that in C5 (17 %). No vaccine-related serious AEs (SAEs) were observed. Seroconversion rates reached 100 % in all three groups 14 days following the first dose. Moreover, the seroconversion rate was 98 %, 96 % and 98 % 12 months following the first dose in T5, C5 and T4, respectively. Both T5 and T4 displayed higher neutralizing antibodies geometric mean concentration (GMC) and geometric mean increase (GMI) compared to those in C5 on day 7, day 14, and 12 months after the first dose, as well as on day 14 after the last dose. There were no significant differences in the incidence of AEs, seroconversion rate, GMC and GMI between T5 and T4. The trial vaccine administered following both Essen regimen and Zagreb regimen shows good safety, immunogenicity and immune persistence, and the trial vaccine is not inferior to the control vaccine. Clinical Trials Registration:NCT03971370.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adolescent / Adult / Allergy and Immunology / Antibodies / Antibodies, Neutralizing - blood / Antibodies, Viral - blood / Bats / Child / Clinical trials / Diploids / diploidy / Disease prevention / Drug dosages / Essen regimen / FDA approval / Female / fever / Freeze Drying / Health care / Healthy Volunteers / Humans / Immune persistence / Immunization / Immunization Schedule / Immunogenicity / Immunogenicity, Vaccine / Lyophilized purified human diploid cells rabies vaccine / Male / Middle Aged / Post-Exposure Prophylaxis - methods / Rabies / Rabies - immunology / Rabies - prevention & control / Rabies Vaccines - administration & dosage / Rabies Vaccines - adverse effects / Rabies Vaccines - immunology / Rabies virus - immunology / Safety / Seroconversion / Vaccination / Vaccines / Young Adult / Zagreb regimen