Safety and immunogenicity of three dose levels of an investigational, highly purified Vero cell rabies vaccine: A randomized, controlled, observer-blinded, Phase II study with a simulated post-exposure regimen in healthy adults

Hum Vaccin Immunother. 2023 Dec 15;19(3):2275453. doi: 10.1080/21645515.2023.2275453. Epub 2023 Nov 3.


A serum-free, highly purified rabies vaccine produced in Vero cells is under development. The initial formulation, PVRV-NG, was evaluated in five Phase II studies and subsequently reformulated (PVRV-NG2). This multicenter, observer-blinded Phase II study investigated the safety and immune response of three different doses (antigen content) of PVRV-NG2 versus a licensed human diploid cell rabies vaccine (HDCV; Imovax rabies®). Healthy adults (N = 320) were randomized to receive PVRV-NG2 (low, medium, or high dose), PVRV-NG, or HDCV (2:2:2:1:1 ratio), according to a five-dose Essen simulated post-exposure regimen (Days [D] 0, 3, 7, 14, and 28). All participants received human rabies immunoglobulin intramuscularly on D0. Immunogenicity was assessed at D0, 14, 28, 42, and 6 months after the final injection using the rapid fluorescent focus inhibition test. Seroconversion rates were calculated as the percentage of participants achieving rabies virus neutralizing antibody titers ≥0.5 IU/mL. All analyses were descriptive. At each timepoint, geometric mean titers (GMTs) increased with antigen content (measured using an enzyme-linked immunosorbent assay). High-dose PVRV-NG2 GMTs were the highest at all timepoints, medium-dose PVRV-NG2 GMTs were similar to those with HDCV, and low-dose PVRV-NG2 GMTs were similar to PVRV-NG. The safety profile of PVRV-NG2 was comparable to PVRV-NG; however, fewer injection site reactions were reported with PVRV-NG2 or PVRV-NG (range 36.7-47.5%) than with HDCV (61.5%). This study demonstrated a dose-effect of antigen content at all timepoints. As post-exposure prophylaxis, the safety and immunogenicity profiles of the high-dose PVRV-NG2 group compared favorably with HDCV. number: NCT03145766.

Keywords: HDCV; Immunogenicity; Vero cell rabies vaccine – serum free; post-exposure prophylaxis; rabies; safety.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Viral
  • Chlorocebus aethiops
  • Humans
  • Rabies Vaccines*
  • Rabies virus*
  • Rabies* / prevention & control
  • Vero Cells


  • Rabies Vaccines
  • Antibodies, Viral

Associated data


Grants and funding

Sanofi was involved in all stages of this study, including study design, data collection, analysis and interpretation, preparation of this article, and decision to submit the article for publication.