DESCRIPTION (provided by the applicant): There are 100 million cases of dengue
infection each year with 250,000 cases of the life-threatening Dengue
Hemorrhagic Fever/Dengue Shock Syndrome (DHS/DSS). Treatment options are
limited to symptoms management. Passive immunoprophylaxis and immunotherapy are
standard treatments for a number of viral diseases. However, the undefined
nature of hyperimmune serum is unsuitable for dengue virus disease treatment.
To provide a defined reagent treatment for severe disease, we propose to
examine the efficacy of using cobra venom factor linked antibodies to the viral
structural envelope (E) and the viral first non-structural (NS1) proteins as
immunotherapeutic agents. In Phase I a combinatorial human Fab library will be
constructed, and Fab fragments which recognize either E or NS1 proteins will be
identified. These fragments will be evaluated for cross-reactivity,
non-overlapping epitope recognition and affinity. All Fab fragments will be
conjugated to cobra venom factor and evaluated for complement mediated
cytolysis and anti-E conjugates for reduction in virus infectivity. To further
evaluate the immunoprophylaxis potential of the conjugates, in vivo mouse
challenge studies will also be performed. In Phase II, F(ab)2-humanized CVF
conjugates will be expressed in mammalian cells and their efficacy evaluated in
mice and non-human primates.
PROPOSED COMMERCIAL APPLICATION:
The dengue virus complex specific anti-E and NS1 Fab fragments identified in Phase I
research have the potential to relieve severe dengue disease symptoms. More than
250,000 annual cases of severe dengue disease are reported each year.
Small Business Information at Submission:
Principal Investigator:Eileen T. Nakano
HAWAII BIOTECHNOLOGY GROUP, INC.
99-193 AIEA HEIGHTS DR, STE 236 AIEA, HI 96701
Number of Employees: