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 specwific 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 attenuated Salmonella as the DNA carrier system. In the last year, we had confirmed that the administration of Salmonella suppressed the allergic symptoms in OVA-sensitized mice. In order to achieve the allergen-specific immune responses, a transcriptional regulatory element from woodchuck hepatitis virus (WPRE) was constructed into the vector to enhance the expression of OVA. The preliminary results indicated some beneficial effects to the mice. Alternatively, OVA protein is expressed with prokaryotic vector and then the attenuated Salmonella can delivery the allergen orally to the sensitized mice. We would like to test other immune-modulatory genes in the established systems in the following years. The results will document some information for the interaction between the immune responses to bacteria and allergens.

Project ID:PG9403-0850
External Project ID:NHRI-EX94-9110SC