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Clinical Trial
. 2024 Jun 14;78(6):1748-1756.
doi: 10.1093/cid/ciae137.

Immunogenicity and Safety of a Purified Vero Rabies Vaccine-Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial

Andrea-Clemencia Pineda-Peña  1 , Qian Jiang  1 , Celine Petit  1 , Joanna Korejwo-Peyramond  2 , Yves Donazzolo  3 , Mathilde Latreille  3 , Marie-Claude Homery  4 , Valerie Babin  1 , Sonia Benamor  1 , Sylvie Pichon  1 , Françoise Guinet-Morlot  1 , Ada-Maria Minutello  1
Affiliations
Clinical Trial

Immunogenicity and Safety of a Purified Vero Rabies Vaccine-Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial

Andrea-Clemencia Pineda-Peña et al. Clin Infect Dis. .

Erratum in

Abstract

Background: A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman-Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®).

Methods: This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was >-5% at D28. Safety was assessed up to 6 months after the last injection.

Results: Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines.

Conclusions: In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines.

Clinical trials registration: NCT03965962.

Keywords: PVRV-NG2; immunogenicity; post-exposure prophylaxis; rabies; safety.

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Conflict of interest statement

Potential conflicts of interest. A. C. P. P., Q. J., C. P., J. K. P., V. B., S. B., S. P., F. G. M., and A. M. M. are employees of Sanofi and may hold shares and/or stock options in the company. Y. D. reports other financial or nonfinancial interests as investigator and CEO of 1 of the investigation sites. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Disposition of participants. *Two participants randomized to receive PVRV-NG2 alone were inadvertently given PVRV-NG2 + HRIG. The difference in N at each visit does not reflect N discontinued, as a small number of participants were absent for 1 visit but completed the active phase by attending an additional visit. One participant was absent for 1 visit and attended the next visit before discontinuation. Abbreviations: D, day; HDCV, human diploid cell vaccine; HRIG, human rabies immunoglobulin; M, month; PVRV, purified Vero cell rabies vaccine; PVRV-NG2, next-generation purified Vero cell rabies vaccine.
Figure 2.
Figure 2.
Percentage of participants achieving RVNA titers ≥0.5 IU/mL at D14, D28, and D42 by vaccination group (per-protocol analysis set). Abbreviations: D, day; HDCV, human diploid cell vaccine; HRIG, human rabies immunoglobulin; PVRV, purified Vero cell rabies vaccine; PVRV-NG2, next-generation purified Vero cell rabies vaccine; RVNA, rabies virus neutralizing antibody.
Figure 3.
Figure 3.
Rabies virus neutralizing antibody GMT at D14, D28, and D42 by vaccination group (per-protocol analysis set). Abbreviations: D, day; GMT, geometric mean titer; HDCV, human diploid cell vaccine; HRIG, human rabies immunoglobulin; PVRV, purified Vero cell rabies vaccine; PVRV-NG2, next-generation purified Vero cell rabies vaccine.
Figure 4.
Figure 4.
Percentage of participants who experienced a solicited injection site reaction (A) or solicited systemic reaction (B) within 7 days after any vaccine injection (safety analysis set). Abbreviations: HDCV, human diploid cell vaccine; HRIG, human rabies immunoglobulin; PVRV, purified Vero cell rabies vaccine; PVRV-NG2, next-generation purified Vero cell rabies vaccine.
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