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Antigenic Chimeric Tick-Borne Encephalitis Virus/Dengue Virus Type 4 Recombinant Viruses

Posted Aug 30 2009 5:00pm

Description of Invention:
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.

Applications:
Development of Tick-Borne Encephalitis Virus vaccines, therapeutics and diagnostics.

Advantages:
Live attenuated chimeric vaccine, known regulatory pathway, potential for lasting immunity with fewer doses.

Development Status:
Vaccine candidates have been synthesized and preclinical studies have been performed.

Inventors:
Alexander G Pletnev (NIAID)
Brian R Murphy (NIAID)
Amber R Engel (NIAID)


Patent Status:
HHS, Reference No. E-078-2009/0
PCT, Application No. PCT/US2010/036678 filed 28 May 2010


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
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 Michael Piziali, NIAID Office of Technology Development, at 301-496-2644 for more information.


Portfolios:
Infectious Diseases
Infectious Diseases - Diagnostics
Infectious Diseases - Vaccines
Infectious Diseases - Research Materials



For Additional Information Please Contact:
Peter Soukas J.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 14,
Rockville, MD 20852-3804
United States
Email: soukasp@mail.nih.gov
Phone: 301-435-4646
Fax: 301-402-0220


Ref No: 2005

Updated: 08/2009

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