Dengue is a mosquito-transmitted acute viral disease of man caused by the Dengue virus, a member of the flaviviridae family. It is endemic in many parts of the world, particularly tropical and sub-tropical regions and quite recently there have been outbreaks in Texas and Hawaii. It has been estimated that there are 100 million new case of Dengue infection per year, up to half a million of which progress to life-threatening Dengue Hemorrhagic Fever. Dengue is classified by NIAID as a re-emerging pathogen and a Category A biodefense agent. Currently there is no vaccine and good management is critical for a successful resolution of the disease. A rapid, accurate diagnosis is the key to clinical decision making. Currently, diagnosis of infection is determined by either IgG or IgM ELISA or PCR. These tests have a number of drawbacks including cost, the time needed to carry them out, the requirement for expensive equipment and their sensitivity and specificity particularly in acute/early stage disease. Hence the need for improved Dengue testing is paramount. InBios International proposes to address this issue by developing a rapid, inexpensive, highly sensitive, point-of-care assay for the detection of viral antigens in the serum of infected individuals. In the pursuit of this objective, we will first identify type-specific Dengue antigens in the sera of patients at different stages of disease by using novel antibody microarrays constructed with a large, unique, panel of anti-dengue Mabs. Once target antigens have been identified we will make lateral flow dipstick assays, or so-called """"""""rapid"""""""" tests with the identified monoclonal antibodies and evaluate their performance in several Dengue-endemic regions (Taiwan, Puerto Rico). The sensitivity of the antigen assay will be increased by the use of a specially constructed, high sensitivity hand held fluorescence reader. We intend that the fluorescence reader will be produced at very low cost. In the pursuit of these goals, InBios will draw on its considerable experience in flavivirus research (we have an FDA approved diagnostic for West Nile Virus) and furthermore has put together a world class team of biomedical scientists with peerless expertise in Dengue pathobiology, diagnostic development and prototype instrument design. ? ? The aims of this application are to develop a specific antigen test for the early diagnosis of Dengue virus infections. This virus is endemic in many tropical and sub-tropical regions of the world and can be fatal. It is also listed as a bioterrorism agent. Early diagnosis could lead to improved treatment outcomes. ? ? ?
| Vaughan, Catherine A; Singh, Shilpa; Grossman, Steven R et al. (2017) Gain-of-function p53 activates multiple signaling pathways to induce oncogenicity in lung cancer cells. Mol Oncol 11:696-711 |
