Seroconversion with Japanese encephalitis vaccine via intradermal route in healthy individuals

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Japanese encephalitis (JE) is a mosquito-borne disease caused by Japanese encephalitis virus (JEV), an arbovirus from the flavivirus genus, family flaviviridae. It is estimated that in 2015 JEV caused more than 100,000 JE cases and 25,000 deaths worldwide. JE is endemic in Asia and Papua New Guinea, and outbreaks have occurred in the Torres Strait Islands. Although the current recommendation is that travellers spending one month or more in endemic regions during the wet season consider vaccination against JEV, there have been many reports of JEV infection in travellers after much shorter trips, including those limited to popular tourist destinations. Effective JE vaccines with low rates of local and systemic adverse events have become available in recent years (e.g. Imojev® [live attenuated recombinant JE vaccine, Sanofi-Aventis], JEspect® [inactivated vero cell vaccine, Valneva). Despite this, the uptake of JE vaccines by travellers remain low. An internal clinical audit of over 1000 medical records at an Australian travel medicine clinic revealed that less than 30% of travellers to JE endemic areas received the vaccine. The high cost of the main vaccine used in Australia (approx. AU$ 300 for Imojev®) is likely to be one of the main reasons for the low uptake. JE vaccines are administered via subcutaneous (SC) or intramuscular (IM) injections; however, intradermal (ID) administration of other vaccines using smaller doses have been shown to be as effective as SC administration for other viruses, e.g. yellow fever (another flavivirus) and rabies. ID administration is widely used for rabies vaccines, and is now recommended by the World Health Organization for both pre- and post-exposure prophylaxis. We conducted a systematic review and meta-analysis and found that the odds of seroconversion after JE vaccine were similar when administered SC or ID (using 20% of SC dose). However, none of the vaccines used in studies included in the meta-analysis are currently available in Australia. The ID route would be certainly less expensive than the SC and IM routes of administration, and potentially increase vaccination uptake among travellers. Therefore, we aim to explore whether ID could potentially be an economical yet effective route of administration for JE vaccine. Our hypothesis is that the seroconversion rate with 0.1ml ID Imojev® (i.e. 20% of the standard SC dose) would be similar to the standard dose of 0.5ml via SC.