Live Attenuated Japanese Encephalitis Virus Vaccine


Japanese encephalitis virus (JEV), a member of the genus flavivirus, is maintained in a zoonotic cycle between Culex mosquitoes and ardeid birds or domestic swine and is responsible for significant epidemics of viral encephalitis in Asia. Three billion people live in regions with endemic JEV transmission resulting in an estimated 60,000 annual cases, of which 20-40% are fatal and 45-70% of survivors have neurologic sequelae. The live-attenuated JEV SA14-14-2 vaccine, produced in primary hamster kidney cells, is safe and effective. Past attempts to adapt this virus to replicate in cells that are more favorable for vaccine production resulted in mutations that significantly reduced immunogenicity. The inventors have isolated 10 genetically distinct Vero cell-adapted JEV SA14-14-2 variants and a recombinant wild-type JEV clone, modified to contain the JEV SA14-14-2 polyprotein amino acid sequence, was recovered in Vero cells. Mutations were also identified that modulated virus sensitivity to type I interferon-stimulation in Vero cells. A subset of JEV SA14-14-2 variants and the recombinant clone were evaluated in vivo and exhibited levels of attenuation that varied significantly in suckling mice, but were avirulent and highly immunogenic in weanling mice and are promising candidates for the development of a second generation, recombinant vaccine.

Potential Commercial Applications: Competitive Advantages:
  • JEV Vaccine
  • JEV Diagnostics
 
  • Safe and efficacious vaccine
  • Extremely low production costs
  • Positive preclinical data
  • Vero cell manufacture


Development Stage:
  • In vitro data available
  • In vivo data available (animal)


Inventors:

Stephen Whitehead (NIAID)  ➽ more inventions...

Gregory Gromowski (NIAID)  ➽ more inventions...


Intellectual Property:
Research Material - Patent protection is not being pursued for this technology.

Publications:
Gromowski G, et al. PMID 25311701
Gromowski G, et al. PMID 25855730

Licensing Contact:
Peter Soukas, J.D.
Email: peter.soukas@nih.gov
Phone: 301-496-2644

OTT Reference No: E-231-2014/0
Updated: Jul 1, 2015