Noninferiority Study of Purified Vero Rabies Vaccine-Serum Free in 3-dose and 2-dose Preexposure Prophylaxis Regimens in Comparison With Licensed Rabies Vaccines.

Abstract

A next-generation, serum-free, highly purified Vero cell rabies vaccine, PVRV-NG2, is in development. This multicenter, observer-blind, phase 3 study evaluated the immunogenicity and safety of PVRV-NG2, compared with 2 licensed rabies vaccines (purified Vero cell rabies vaccine [PVRV] and human diploid cell vaccine [HDCV]), as a preexposure prophylaxis (PrEP) regimen. Participants were randomized 3:1:1 to PVRV-NG2, PVRV, or HDCV, as a 3-dose (cohort 1; children and adults; day [D] 0, D7, and D28) or 2-dose (cohort 2; adults; D0 and D7) PrEP regimen. The primary objective was noninferiority of PVRV-NG2 to PVRV and HDCV as 3-dose PrEP, based on the proportion of participants with rabies virus-neutralizing antibody titer ≥0.5 IU/mL at D42. Noninferiority of immune responses for 2-dose PrEP at D28 and noninferiority of 2-dose (D28) versus 3-dose (D42) HDCV were also assessed as secondary immunogenicity objectives. Safety was assessed throughout. Overall, 1708 participants were enrolled (cohort 1: 505 children, 505 adults; cohort 2: 698 adults). All participants had rabies virus-neutralizing antibody titers ≥0.5 IU/mL after 3-dose PVRV-NG2 (D42), with noninferiority to PVRV and HDCV demonstrated. All secondary immunogenicity objectives were achieved, including noninferiority of 2-dose PVRV-NG2 versus 2-dose PVRV and HDCV (D28) and 3-dose HDCV (D42), and noninferiority of 2-dose HDCV versus 3-dose HDCV. The safety profile of PVRV-NG2 was comparable to those of PVRV and HDCV. This study supports the use of PVRV-NG2 in 2- or 3-dose PrEP regimens, with no safety concerns identified. ClinicalTrials.gov identifier: NCT04127786; EudraCT: 2019-000973-22; WHO: U1111-1217-3241.