Abstract
Cockroaches produce potent allergens that are an important cause of asthma. The hallmark feature of allergic asthma is abnormal expansionof Th2 cells in the lungs. We present a novel immunotherapeutic strategy using a Bla g 1 DNA vaccination that prevents lung inflammation, airwayobstruction, and hyperreactivity to allergen in a mouse modelof allergic disease, even afteranimals were presensitized and a Th2‐polarized immune responsewas established. Animals which received the DNA vaccine were protected against a following allergic sensitization with cockroach extract. The protective effect was characterized by suppression of cockroach allergen‐specific IgE production and enhanced IFN‐γ expression. In a therapeutic situation, treatment of sensitized animals with DNA vaccines decreased IgE production and drastically reduced anaphylactic activity as measured by enhanced IFN‐γ expression. Concerning the cellular immune response, DNA immunization induced a sustaining and dominant shift from a Th2 type response towards a balanced Th1/Th2 type response as indicated by increased IFN‐γ but decreased IL‐4 and IL‐5 levels in lymphoproliferation assays. Moreover, studies using bronchoalveolar lavage fluids of cockroach‐sensitized animals showed marked increase in imflammatory cells and eosinophils in contrast to BALF from Blag 1‐vaccinated animals. The histologic studies showed that the much reduced infiltration of inflammatory cells was observed in lung tissue of the gene vaccinated mice than that of the controls mice. The results demonstrate the allergen‐specific protective and therapeutic efficacy of a DNA vaccine encoding the cockroach allergen Bla g 1.
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