Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

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Abstract
DNA-based immunization represents an attractive alternative approach to the current treatment of allergic diseases by specific immunotherapy with allergen extracts. In this study, we used a replication-deficient adenovirus vector (AdCMV), to examine the in vivo efficacy of preventive and therapeutic genetic immunization in a mouse model of type I allergy. Primary immunization with a recombinant adenovirus expressing the model antigen β-galactosidase (AdCMV-βgal) induced a Th1 immune response (predominance of IgG2a antibodies, high frequency of IFN-γ producing T cells) and large numbers of cytotoxic T lymphocytes. Prophylactic vaccination with AdCMV-βgal abolished the production of specific IgE following subsequent immunization with βgal-protein, and skewed the Th2-biased immune response to a Th1-orientated response. In contrast, therapeutic administration of AdCMV-βgal after priming with βgal-protein neither significantly inhibited ongoing IgE production nor modulated a manifest Th2 immune response. Thus, allergen gene transfer via recombinant adenovirus represents an effective method to establish protection against the development of allergic disorders, but does not qualify as a therapeutic tool to interfere with ongoing high IgE production.