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Clinical Trial
. 2023 Dec 15;19(3):2275453.
doi: 10.1080/21645515.2023.2275453. Epub 2023 Nov 3.

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

Sylvie Pichon  1 , Francoise Guinet-Morlot  2 , Jamshid Saleh  3 , Brandon Essink  4 , Andrea-Clemencia Pineda-Peña  1 , Annick Moureau  1 , Celine Petit  1 , Ada-Maria Minutello  1
Affiliations
Clinical Trial

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

Sylvie Pichon et al. Hum Vaccin Immunother. .

Abstract

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. Clinicaltrials.gov number: NCT03145766.

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

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Conflict of interest statement

JS and BE declare they have no conflicts of interest. SP, FGM, ACPP, AM, CP, and AMM are employees of Sanofi.

Figures

Figure 1.
Figure 1.
Participant flow from visits 1–8 for all groups.
Figure 2.
Figure 2.
Post-vaccination geometric mean rabies virus neutralizing antibody (RVNA), determined by RFFIT (modified full analysis set).
Figure 3.
Figure 3.
Post-vaccination: rabies virus neutralizing antibody (RVNA) titers determined by RFFIT≥0.5 IU/mL (per-protocol analysis set).
See this image and copyright information in PMC

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