Abstract
Japanese encephalitis (JE) is a significant human health concern in Asia, Indonesia and parts of Australia with more than 3 billion people potentially at risk of infection with Japanese encephalitis virus (JEV), the causative agent of JE. Given the risk to human health and the theoretical potential for JEV use as a bioweapon, the development of safe and effective vaccines to prevent JEV infection is vital for preserving human health. The development of vaccines for JE began in the 1940s with formalin-inactivated mouse brain-derived vaccines. These vaccines have been shown to induce a protective immune response and to be very effective. Mouse brain-derived vaccines were still in use until May 2011 when the last lots of the BIKEN(®) JE-VAX(®) expired. Development of modern JE vaccines utilizes cell culture-derived viruses and improvements in manufacturing processes as well as removal of potential allergens or toxins have significantly improved vaccine safety. China has developed a live-attenuated vaccine that has proven to induce protective immunity following a single inoculation. In addition, a chimeric vaccine virus incorporating the prM and E structural proteins derived from the live-attenuated JE vaccine into the live-attenuated yellow fever 17D vaccine virus backbone is currently in clinical trials. In this article, we provide a summary of JE vaccine development and on-going clinical trials. We also discuss the potential risk of JEV as a bioweapon with a focus on virus sustainability if used as a weapon.
Highlights
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus (Family Flaviviridae, Genus Flavivirus) endemic to Eastern and Southern Asia and Indonesia and has been isolated in Northern parts of Australia
A disease similar to Japanese encephalitis (JE) was first described in the late 1800s, but the first clearly identified epidemic occurred in Japan in 1924 with a second large epidemic in 1935 [1]
In 1995 JEV was identified in a human case in the Torres Strait region of Australia [4] with a subsequent incursion into the Cape York area of mainland Australia in 1998 [5]
Summary
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus (Family Flaviviridae, Genus Flavivirus) endemic to Eastern and Southern Asia and Indonesia and has been isolated in Northern parts of Australia. The potential for local JE outbreaks near small farms or piggeries remains a risk if the virus is introduced and competent vectors are present in sufficient numbers to facilitate efficient transmission of the virus Large water birds such as herons and egrets play an important role in the transmission cycle of JEV as they can develop sufficiently high viremia to allow infection of a biting mosquito and their wide migratory range can allow dissemination of the virus [54,55,56]. The KD-287 (JEIMMUGEN INJ.) (produced by Kaketsuken) vaccine is based on the Beijing-1 strain of JEV This vaccine has been licensed for use in Japan and is currently undergoing additional clinical trials in children in Korea. Most of these trials involved adult volunteers, but several ongoing phase II and phase III clinical trials involve both adults and children > 9 months of age (www.clinicaltrials.gov)
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