SBIR-STTR Award

Japanese encephalitis virus (JEV) is a major health problem in the world. Each year 50,000 cases of Japanese encephalitis are reported officially and more than 30% are fatal. Development of effective, safe and economical JEV vaccines for human use is necessary. A highly attenuated recombinant JEV, IC47, has been generated using a system for recovering viruses from infectious RNA transcribed from cDNA templete (infectious cDNA clones). This virus has potential for used as a human live vaccine since: I) it is highly attenuated in mice, 2) it is highly immunogenic, 3) immunization with the 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 is reasonable, and 8) manufacturing methods are established. In this Phase I project, the infectious clone system will be used to introduce multiple mutations in the IC47 genome to stabilize the attenuation phenotype. Neurovirulence and immunogenicity of the modified virus are studied in mice.Awardee's statement of the potential commercial applications of the research:A significant market exists for JEV vaccines that includes several million travelers/year in the US and Europe and 40 million children/year in JEV-endemic regions. The killed mouse-brain JEV vaccine now available in the US and Europe is costly and requires 3 doses. It is too expensive for use in Asia, except in the most affluent countries. We will develop and commercialize an inexpensive, live attenuated, single-dose vaccine.National Institute of Allergy and Infectious Diseases (NIAID)

The objective of this project is to develop a safe, efficacious, single- dose, cost-effective vaccine for protection of humans against disease caused by Japanese encephalitis virus (JEV). A genetically defined, live attenuated vaccine will be developed by the introduction of specific mutations into a cDNA clone of JEV. The infectious clone system will be used to identify and introduce two other independent attenuating mutations into the JEV gene to reduce the risk of reversion. The resulting recombinant virus with triple attenuating amino acid substitutions, will be characterized biologically, with respect to stability, virulence, transmissibility and immunogenicity. Replication in cell cultures approved for manufacture of human products will be defined, and master and manufacturer's working seeds and pilot lots of vaccine prepared under GMP. Safety, immunogenicity and protection tests will be performed in monkeys. At the completion of the work to be funded under this proposal, it is anticipated that the vaccine candidate will be ready for initial clinical trials.Proposed Commercial Applications:JE is a major health threat in Asia. Licenses inactivated vaccines are too expensive to produce and distribute (they require multiple doses) for routine use in most Asian countries. The vaccine developed in this program would be used for routine childhood immunization in Asia. The estimated market for a single dose childhood JE vaccine in Asia exceeds $400 MM/year. A substantial marked (>$100 MM/year) also exists for US and European travelers to Asia and for US Military.