DOI: 10.1093/cid/ciae137 ISSN: 1058-4838

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

Andrea-Clemencia Pineda-Peña, Qian Jiang, Celine Petit, Joanna Korejwo-Peyramond, Yves Donazzolo, Mathilde Latreille, Marie-Claude Homery, Valerie Babin, Sonia Benamor, Sylvie Pichon, Françoise Guinet-Morlot, Ada-Maria Minutello
  • Infectious Diseases
  • Microbiology (medical)
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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 III study in France evaluated immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG), compared with 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 receive PVRV-NG2+HRIG, PVRV+HRIG, HDCV+HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, 3, 7, 14, and 28, with HRIG administered 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

The 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.

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