DNA Carrier with OVA or Immune-Modulators to Asthmatic Mice

Bronchial asthma is a chronic inflammatory disorder of the airways. It has been well established that cytokines produced by Th2 type cells are responsible for asthmatic pathology. Despite intensive effort designed to develop pharmacological agents to block inflammatory mediators, therapeutic strategy with long-term benefits has not been available. Direct DNA injection of allergen genes has been proposed to enhance specific Th1 response and showed some encouraging results in sensitized animals. Alternatively, genes carried by attenuated Salmonella bacteria have been tested as vaccine systems in the treatment of infectious diseases and tumors. Higher antigen-specific Th1 activity was also observed. With the established murine asthmatic model using chicken ovalbumin (OVA) as allergen, we will investigate the possible oral vaccine and therapeutic strategy with the use of Salmonella as the DNA carrier system. Two types of immune-modulatory genes that will be examined in this project are Th1-enhancing cytokine, such as interferon-g (IFN-g) or interleukin-12 (IL-12), and co-stimulatory molecule, such as B7-1, B7-2, or antisense directed to B7-2. In addition, IL-4 inducible promoters, from Stat6 and Dectin genes, will be constructed to replace constitutively expressed CMV promoter to drive allergen, Th1-cytokines or B7-1/ B7-2 genes. This may prevent the over-expressing of allergen or immune-modulator genes. The usage of internal ribosome entry site (IRES) will ensure the co-expression of OVA and immune-modulatory genes. The results obtained in this study will allow us to understand the mechanisms of T cells responding to allergen and regulatory genes in vivo, following the administration of transformed Salmonella. A novel vaccine or therapeutic approach can be developed based on the information obtained from this study

Project ID:PG9303-1448
External Project ID:NHRI-EX93-9110SC