An overview of the immunogenicity and effectiveness of current human rabies vaccines administered by intradermal route

Pre- as well as post-exposure prophylaxis plays an important role in controlling the number of deaths associated with human rabies. Rabies vaccines, classically injected intramuscularly, are now also administered by intradermal (ID) route. Vaccines to be administered by the ID route should meet the same quality, safety and efficacy specifications as vaccines for intramuscular (IM) use. The aim of this paper is to provide information based on publicly available data regarding the ID use of rabies vaccines and to identify potential needs for further analysis of the potency, immunogenicity and effectiveness of rabies vaccines administered by this route. A first literature search, focused on the immunogenicity of rabies vaccines given by ID route, identified 338 publications in the period 1997-2018, 40 of which were included in our analyses. A second search investigating the effectiveness of ID vaccination resulted in 371 hits for the period 2007-2018, of which 13 suitable publications were retained. The immunogenicity of current rabies vaccines was analyzed in 3 ways: proportion of subjects reaching the antibody threshold of 0.5 IU/ml after ID vaccination, relationship between potency and immunogenicity of the vaccine given intradermally, and comparison of antibody responses after IM or ID vaccination. Overall, vaccines administered intradermally were found immunogenic. Post-exposure prophylaxis by ID route appeared at least as immunogenic as by IM regimens. By contrast, ID pre-exposure prophylaxis trended towards lower antibody titers than IM vaccination, but the observation was not associated with any clinical relevance. Vaccine effectiveness was assessed by investigating survival after exposure. Data from more than 30,000 patients who sought rabies post-exposure prophylaxis did not indicate that current vaccines administered by ID route lack efficacy. These results support current recommendations for ID vaccination against rabies. However, published data on ID performance were associated with significant weaknesses that future research should better address. (C) 2018 Published by Elsevier Ltd.