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.