Immunogenicity and safety of serum-free rabies vaccine for human use with simulated post-exposure schedules: A randomized, double-blind, active-controlled phase III clinical trial

BACKGROUND: Rabies is a fatal zoonotic disease that can be effectively prevented through timely postexposure prophylaxis (PEP). Serum-free rabies vaccines may theoretically reduce risks associated with animal-derived components, and simplified PEP schedules may improve vaccination compliance and accessibility. This trial evaluated the immunogenicity and safety of Sinovac serum-free rabies vaccine administered using 5-dose and simplified 4-dose schedules. METHODS: A randomized, double-blind, active-controlled phase III clinical trial was conducted in 2000 healthy participants aged 10-60 years. Participants were randomized in a 1:1:1:1 ratio to receive Sinovac rabies vaccine according to the 5-dose Essen schedule on D0,3,7,14,28 (5-dose study group), two 4-dose schedules on D0,3,7,14 (4-dose study group 1) or D0,3,7,28 (4-dose study group 2), or a licensed rabies vaccine according to the 5-dose Essen schedule (5-dose control group). Primary endpoints were seroconversion rates (SCRs) and geometric mean concentrations (GMCs) on D14 and SCRs on D42 in susceptible participants with baseline rabies virus neutralizing antibodies (RVNA) <0.5 IU/mL. Secondary endpoints included SCR and GMC on D28, seropositive rates at 3 and 6 months, and safety through 6 months. RESULTS: In susceptible participants, SCRs reached 100% on D14, D28, and D42 in all groups. On D14, RVNA GMCs were 34.71, 36.36, 33.17, and 37.38 IU/mL in the two 4-dose study groups, 5-dose study group, and the control group, respectively. All three Sinovac vaccine groups met the prespecified non-inferiority criteria versus the control group for D14 and D42 SCRs and D14 GMCs. Seropositive rates remained 100% at 3 months and above 97% at 6 months in all Sinovac vaccine groups. Safety profiles were comparable across groups, and most adverse reactions were Grade 1, with no vaccine-related serious adverse events reported. CONCLUSIONS: Sinovac serum-free rabies vaccine induced rapid, robust, and persistent immune responses under both 5-dose and simplified 4-dose schedules, with a favorable safety profile.