Arbovax

Arbovax intends to follow a different strategy to those currently used for vaccine production. Using the patented technology developed by Drs. Brown and Hernandez at NC State University the company will develop a mutant virus that will be produced in insect cells and that is normal in its size, shape, immunological and functional properties. This virus will replicate as well as the parent wild-type virus in the insect host. It will infect the mammalian host and viral proteins will be produced in the infected cell. However because the virus glycoprotein cannot integrate properly into the mammalian membrane, no infectious progeny virus will be produced in mammalian cells. Because the mutant is a deletion mutant there is little chance for reversion to wild-type phenotype, a common problem with attenuated viral vaccines.

To fully protect against all sub-types of Dengue virus a tetravalent vaccine will be required. Vaccination against any single serotype greatly increases the risk of developing hemorrhagic fever upon subsequent infections. The process of producing a tetravalent vaccine will be started with a full length cDNA clone of Dengue virus type 2.

Current Development Initiatives
To fully protect against all sub-types of Dengue virus a tetravalent vaccine will be required. Vaccination against any single serotype greatly increases the risk of developing hemorrhagic fever upon subsequent infections. The process of producing a tetravalent vaccine will be started with a full length cDNA clone of Dengue virus type 2.

Dengue Fever

Current production of the Dengue type 2 constructs by Arbovax scientists is underway at our Raleigh NC facility. These construct will be tested in a mouse model, in collaboration with Immunobiosciences, as part of the collaborative research agreement. Confirmatory work will use a primate model. Mouse studies began 28th August 2008.

Work on constructs for Dengue type 1, 3 and 4 will be undertaken by Arbovax up to and including testing in a mouse model. Upon the successful conclusion of this work testing of these constructs will then be transferred for primate work and eventual formulation of a complete vaccine comprising all four serotypes. [ more on Dengue Fever ]

As part of a Collaborative Research and Development Agreement (CRADA) with the US Army the pilot bioproduction facility at WRAIR in Silver Spring MD will be used for pilot lot production. The US Army also has a primate colony that Arbovax can access under the agreement. Phase 1 clinical trials are also covered and the US Army has decades of experience in this area.

Prior to or upon the successful conclusion of primate studies, Arbovax intends to enter in to corporate partnership(s) for the formulation phase of an optimized vaccine containing all four serotypes and subsequent human trials.

Other Targets
Arbovax is currently working with Dr. Brown’s group, using the NC State BL-3 facility, in developing clones of West Nile, and Chikungunya which have the potential to significantly broaden the company’s portfolio of vaccine targets.

Chikungunya Fever

Chikungunya (an Alphavirus) is a viral illness that is spread by the bite of infected mosquitoes. The disease resembles dengue fever, and is characterized by severe, sometimes persistent, joint pain (arthritis), as well as fever and rash. The widespread occurrence of this disease causes substantial morbidity and economic loss. Although typically found in the southern part of India, recent press identified outbreaks in Europe during 2007. (Science Feb 6 2008)

West Nile Virus (WNV)

WNV is known to have extensive distribution throughout Africa, the Middle East, parts of Europe, Russia, south and central Asia, and Australia. In addition, the virus has spread rapidly through North America, the Caribbean, and Mexico. Controlled studies to evaluate specific therapies for WN virus infection have not been completed. A Phase I trial to assess the safety and efficacy of intravenous immune globulin containing high titers of antibody to WN virus is in progress, as is a similar trial using interferon-?-n3. A trial of interferon- ?-2a was unsuccessful.

Veterinary Market
There is a significant market for vaccines against equine encephalitis which is an Alphavirus as well as many other diseases that affect livestock. The less stringent regulatory pathway to market makes this an interesting project to run in parallel with the Dengue development. Arbovax intends to pursue this work as time and finances permit while not diluting the focus on Dengue Fever. Longer term the company may seek specific funding from sources focused on animal health, including horses and pigs.

Arbovax currently has an exclusive license for the following foundational issued patents as well (and their foreign counterparts) giving broad protection to the underlying technology:

These issued patents give Arbovax the freedom to apply their technology for viral modification to all arboviruses including alphaviruses, bunyaviruses and flaviviruses.
The potential exists for the development of follow-on intellectual property for specific vaccine formulations and uses for specific disease indications, further bolstering the proprietary position of the Company’s technology.