評估利用超音速流動力皮下遞送裸露Der p 2去氧核醣核酸疫苗抑制歐洲室塵蟎誘導之呼吸道發炎之效力

Abstract

Dermatophagoides pteronyssinus group 2 (Der p 2) is a major allergen to induce allergic asthma, and is a good candidate for DNA vaccine development. Previous study suggested that intramuscular injection of plasmid DNA containing wild type Der p 2 gene induced Th1 skewed immune response. Our previous study demonstrated that novel gene gun delivering naked DNA through supersonic flow elicited similar levels of antibody and cellular response with lower dose of DNA plasmid in comparison with intramuscular injection. In addition, administration of naked DNA via novel gene gun induced a stronger Th1-skewed effect on the development of antigen-specific immune responses than traditional delivery of gold coated DNA vaccine. We focused on efficacy evaluation of naked Der p 2 DNA vaccine delivered into skin by supersonic flow for suppression of Dermatophagoides pteronyssinus- induced airway inflammation in comparison with intramuscular injection. After sensitization intraperitoneally with Der p crude extract, Balb/c mice were inoculated with naked DNA vaccine encoding Der p2 antigen by novel gene gun or intramuscular injection to protect the allergen challenges. Lung function and histological studies showed that the group of novel gene gun and intramuscular injection both reduced the airway hypersensitivity and downregulated airway inflammation. Furthermore, the vaccinated mice by gene gun showed a significant suppressed the induction of Der p and Der p2 specific immunoglobulin synthesis compared to the group of intramuscular injection. According to analysis of cell surface marker staining for intracellular cytokines, the group of gene gun had higher numbers of IFN-gamma secreting CD4 and IFN-gamma secreting CD8 T cells than intramuscular injection and significantly attenuated the numbers of IL-4 secreting CD4 T cells in spleen cells. Thus, we suggest that novel gene gun significantly increases the Der p 2-specific anti-airway inflammation Th1 immune response and has better efficacy to protect the asthmatic antigen exposures than intramuscular administration. The results also provided the immunological rationale for testing delivery of naked Der p 2 DNA vaccine into skin via novel gene gun in patients with Dermatophagoides pteronyssinus induced airway inflammation.