Inhibition of allergic inflammation in the lung by plasmid DNA allergen immunization.

The nature of the immune response (Th1/Th2) in mice to protein antigens or allergens was compared to that of immunization with pDNA encoding the same antigens. pDNA immunization induced a Th1 response and no IgE antibodies whereas the proteins induced a Th2 response and IgE antibodies. Furthermore, the pDNA induced Th1 response dominated over the protein elicited Th2 response in a secondary immune response. In particular, a preexisting Th2 response (as is the case in allergic patients) did not prevent a new Th1 response to an allergen-pDNA booster injection. The major reason why pDNA immunization induced a Th1 response to allergens was the presence of immunostimulatory non-coding DNA sequences (ISS) in the plasmid constructs having a CpG motif. These ISS caused antigen presenting cells to secrete INF-alpha, INF-beta and IL-12, all cytokines that induce naive T cells to differentiate into CD4+ Th1 cells and CD8+ Tc1 cells. Passive transfer of both Th1 and Tc1 cells from pDNA immunized mice into naive mice inhibited a Th2 response and IgE antibody formation to a subsequent injection of allergen in alum. pDNA immunization or ISS-oligonucleotide injection prior to allergen challenge reduced both immediate type airway sensitivity and late phase allergen induced eosinophil filtration of the lung. Allergen-pDNA immunization may provide a novel type of immunotherapy for the treatment of allergic diseases in man. Since only small amounts of allergen are secreted by the allergen-pDNA transformed cells, allergen-pDNA immunotherapy will unlikely carry the risk of the anaphylactic reactions that are associated with classical allergen injection immunotherapy.