Antigenic Chimeric Tick-Borne Encephalitis Virus/Dengue Virus Type 4 Recombinant Viruses
The tick-borne encephalitis virus (TBEV) complex is a group of viruses that can cause severe neutrotropic disease and up to thirty percent (30%) mortality. While these viruses can be found in many parts of the world, the largest impact of the disease occurs in Europe and Russia, where approximately fourteen thousand (14,000) hospitalized TBEV cases occur annually. TBEV is in the family Flaviviridae, genus flavivirus and is composed of a positive-sense single stranded RNA genome that contains 5' and 3' non-coding regions and a single open reading frame encoding ten (10) proteins. At present, a vaccine or FDA approved antiviral therapy is not available.
The inventors have previously developed a WNV/Dengue4Delta30 antigenic chimeric virus as a live attenuated virus vaccine candidate that contains the WNV premembrane and envelope (prM and E) proteins on a dengue virus type 4 (DEN4) genetic background with a thirty nucleotide deletion (Delta30) in the DEN4 3'-UTR. Using a similar strategy, the inventors have generated an antigenic chimeric virus, TBEV/DEN4Delta30. This chimeric virus also contains attenuating mutations within the E and nonstructural NS5 proteins. Preclinical testing results with the derived virus indicate that chimerization of TBEV with DEN4Delta30 and introduction of the attenuating mutations decreased neuroinvasiveness and neurovirulence in mice. The TBEV/DEN4delta30 vaccine candidate was safe, immunogenic, and provided protection in monkeys against challenge with TBE viruses.
This application claims live attenuated chimeric TBEV/DEN4Delta30 vaccine compositions. Also claimed are methods of treating or preventing TBEV infection in a mammalian host, methods of producing a subunit vaccine composition, isolated polynucleotides comprising a nucleotide sequence encoding a TBEV immunogen, methods for detecting TBEV infection in a biological sample and infectious chimeric TBEV.
|Potential Commercial Applications:||Competitive Advantages:||Development of Tick-Borne Encephalitis Virus vaccines, therapeutics and diagnostics.||Live attenuated chimeric vaccine, known regulatory pathway, potential for lasting immunity with fewer doses.|
Alexander Pletnev (NIAID)
Brian Murphy (NIAID)
Amber Engel (NIAID)
US Application No. 13/322,317
PCT Application No. PCT/US2010/036678
US Application No. 61/181,982
US Application No. 14/014,920
The NIAID is seeking statements of capability or interest from parties interested in collaborative research in preclinical study of the long-term immunity induced by the TBEV/DEN4 vaccine candidate against highly virulent TBE viruses and in the clinical trials of this vaccine in humans. Please contact Maryann Puglielli, NIAID Office of Technology Development, at 301-496-2644 for more information.
Peter Soukas , J.D.
NIH Office of Technology Transfer
OTT Reference No: E-078-2009/0