Gene immunization for allergic disorders
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For immunotherapy to regain a major role as a treatment for allergic disorders, improvements in current allergen immunotherapy are needed to decrease treatment-associated risks when compared to the risks involved in current pharmacological management protocols . The recent findings described in this review suggest that there is potential for the development of a novel form of immunotherapy, i.e., allergen gene vaccination, which would be safe and effective. Gene vaccination does not result in inflammation when injected 11.d and has been shown to down-regulate antigen-specific IgE antibodies in mice and rats, and in the reduction of late phase allergic responses. The presence of ISS-containing DNA in the vaccine formulation, whether within the pDNA expression vectors, or co-injected, is important in the induction of IFN-γ-mediated Th1 cell differentiation, IL-5 inhibition, and B cell isotype switching, which cumulatively may lead to the reduction of allergic responses (Fig. 4).
To date, all the in vivo experiments showing IgE inhibition have been performed in mice and rats. However, based on the combined observations that pDNA is also taken up by human skin cells transplanted onto nude mice , and that ISS-containing DNA induces Th1-promoting cytokines from human PBMC, it is possible that the antiallergic responses observed in rodents will also occur in human. As for safety considerations, in vitro data indicate that the transfected cells secrete low levels of antigen which are unlikely to induce the anaphylactic reactions seen in vivo with classical immunotherapy. Furthermore, the allergens encoded by pDNA constructs can be designed to include a transmembrane domain and anchor, thereby preventing the secretion of allergen and possible induction of anaphylactic reactions.
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