Genetic Engineering of Japanese Encephalitis Virus

Japanese encephalitis virus (JEV) is a major health problem in the world. Each year 50,000cases of Japanese encephalitis are reported officially and more than 30% are fatal. Development ofeffective, safe and economical JEV vaccines for human use is necessary. A highly attenuatedrecombinant JEV, IC47, has been generated using a system for recovering viruses from infectious RNAtranscribed from cDNA templete (infectious cDNA clones). This virus has potential for used as a humanlive vaccine since: 1) it is highly attenuated in mice; 2) it is highly immunogenic, 3) immunization withthe virus protects mice from lethal virulent JEV infection, 4) infected mice do not develop viremia, 5)it is molecularly defined, 6) seed virus can be generate from cDNAs, 7) the cost for the vaccine isreasonable, and 8) manufacturing methods are established. In this Phase I project, the infectious clonesystem will be used to introduce multiple mutations in the IC47 genome to stabilize the attenuationphenotype. Neurovirulence and immunogenicity of the modified virus are studied in mice.