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

• Published in: Clinical infectious diseases Vol. 78; no. 6; pp. 1748 - 1756
• Main Authors: Pineda-Peña, Andrea-Clemencia, Jiang, Qian, Petit, Celine, Korejwo-Peyramond, Joanna, Donazzolo, Yves, Latreille, Mathilde, Homery, Marie-Claude, Babin, Valerie, Benamor, Sonia, Pichon, Sylvie, Guinet-Morlot, Françoise, Minutello, Ada-Maria
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 14-06-2024
• Subjects: Adolescent; Adult; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Chlorocebus aethiops; Double-Blind Method; Female; France; Healthy Volunteers; Humans; Immunogenicity, Vaccine; Major; Male; Middle Aged; Post-Exposure Prophylaxis - methods; Rabies - prevention & control; Rabies Vaccines - administration & dosage; Rabies Vaccines - adverse effects; Rabies Vaccines - immunology; Rabies virus - immunology; Vero Cells; Young Adult; France; rabies; PVRV-NG2; post-exposure prophylaxis; safety; immunogenicity
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciae137

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.
The next-generation rabies vaccine PVRV-NG2, demonstrated immunogenic non-inferiority versus standard-of-care vaccines and a favorable safety profile when co-administered with human rabies immunoglobulin or as a stand-alone vaccine in a simulated post-exposure prophylaxis, phase 3 trial in healthy adults.
Graphical Abstract
Graphical Abstract