Purified Vero cell rabies vaccine (PVRV, Verorab): A review of intradermal use between 1985 and 2019

Abstract

Background: Worldwide, rabies continues to kill roughly 59,000 individuals per year. Rabies vaccine types and regimens have changed over time, including the recent World Health Organization (WHO) update to include intradermal (ID) administration for rabies post-exposure prophylaxis (PEP). A trend has developed in the rabies field in which both the dose number and dose volume is reduced to accommodate patients and vaccine supply constraints, especially in underserved endemic regions. Methods & Materials: In light of this critical health issue and an evolving environment of vaccination, we sought to perform a full literature review of PEP and pre-exposure prophylaxis (PrEP) PVRV vaccination via ID administration. The ID route endorsed by WHO was already included in Verorab product insert since 1996 in several Asian countries, whereas the intramuscular (IM) route was first registered worldwide over 30 years ago. The review searched 7 databases (including the terms: rabies vaccine, PrEP, PEP, and ID) and was enriched with non-published data, thus covering a variety of schedules including company-sponsored or externally-conducted studies. Results: A total of 34 studies out of 136 original references were identified, including over 3000 subjects and related to no less than 10 PrEP and 17 PEP regimens, including booster administration. In all studies, seroconversion rate (SCR) was assessed by the proportion (%) of vaccines with RVNA titers ≥0.5 IU/mL. SCR was assessed from day (D) 0 to Year (Y) 5, including in general D14, D28 and Y1 and Y1 + D7 and/or D14 data for schedules with booster. For PrEP, 10 studies including around 900 subjects were identified and documented schedules from 1D to 3 visits, through 1 month resulting in SCR higher than 90%. PEP was documented in 24 studies including more than 2150 subjects. D14 SCR ranged from 70% (in HIV CD4 <200 mm3 patients) to 100%. All schedules including booster(s) at Y1 resulted in 100% SCR 7 and/or 14 days after it. Conclusion: ID administration of rabies vaccination is efficacious and future studies will help confirm this regarding PVRV PrEP ID delivery through abbreviated, updated WHO schedules.