The Route of Administration of Rabies Vaccines: Comparing the Data

Deborah J Briggs,Susan M Moore

doi:10.3390/v13071252

Abstract

Cell culture rabies vaccines were initially licensed in the 1980s and are essential in the prevention of human rabies. The first post-exposure prophylaxis (PEP) vaccination regimen recommended by the World Health Organization (WHO) was administered intramuscularly over a lengthy three-month period. In efforts to reduce the cost of PEP without impinging on safety, additional research on two strategies was encouraged by the WHO including the development of less expensive production methods for CCVs and the administration of reduced volumes of CCVs via the intradermal (ID) route. Numerous clinical trials have provided sufficient data to support a reduction in the number of doses, a shorter timeline required for PEP, and the approval of the intradermal route of administration for PEP and pre-exposure prophylaxis (PreP). However, the plethora of data that have been published since the development of CCVs can be overwhelming for public health officials wishing to review and make a decision as to the most appropriate PEP and PreP regimen for their region. In this review, we examine three critical benchmarks that can serve as guidance for health officials when reviewing data to implement new PEP and PreP regimens for their region including: evidence of immunogenicity after vaccination; proof of efficacy against development of disease; and confirmation that the regimen being considered elicits a rapid anamnestic response after booster vaccination.

Highlights

Rabies is a zoonotic disease with up to 99% of human rabies deaths caused by exposure to infected dogs [1]
Several successful mass canine vaccination programs in canine rabies endemic countries have proven that elimination of canine rabies is feasible, and it is cost effective in preventing human rabies deaths [2,3,4]
The sheer abundance of the published data associated with the IM and ID routes of administration can make it difficult to compare these data when attempting to make changes to national rabies vaccination regimens for human rabies prevention. This brief review examines three critical factors that should be included in the evaluation process when it is necessary to compare clinical data from IM and ID administration of Cell culture rabies vaccines (CCVs). These factors include evidence of rabies virus neutralizing antibodies (RVNAs) after vaccination, proof that the regimen under consideration protects patients exposed to confirmed rabid animals, and confirmation that an anamnestic response to booster vaccination occurs in persons that have received pre-exposure prophylaxis (PreP)

Summary

Introduction

Rabies is a zoonotic disease with up to 99% of human rabies deaths caused by exposure to infected dogs [1]. The sheer abundance of the published data associated with the IM and ID routes of administration can make it difficult to compare these data when attempting to make changes to national rabies vaccination regimens for human rabies prevention This brief review examines three critical factors that should be included in the evaluation process when it is necessary to compare clinical data from IM and ID administration of CCVs. This brief review examines three critical factors that should be included in the evaluation process when it is necessary to compare clinical data from IM and ID administration of CCVs These factors include evidence of rabies virus neutralizing antibodies (RVNAs) after vaccination, proof that the regimen under consideration protects patients exposed to confirmed rabid animals, and confirmation that an anamnestic response to booster vaccination occurs in persons that have received pre-exposure prophylaxis (PreP)

Comparing the Data

Immunogenicity

Efficacy

Anamnestic Response

Findings

Conclusions