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. Three days after the oral administration of the attenuated Salmonella, live bacteria had been recovered from spleen, Peyer？HHHH？HHHHs patch and mesenteric lymph nodes. However, no significant OVA or GFP expression was detected in mice receiving transfected Salmonella. Moreover, we did not detect higher or Th1-prone responses from the cells of those peripheral organs. We then will try to use different strains of attenuated Salmonella or vectors with different backbones. An alternative delivery system with intro-muscular injection combined with electroporation is also tested to delivery the antigens.

Project ID:PG9203-0560
External Project ID:NHRI-EX92-9110SC