Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy.
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 beta-galactosidase (AdCMV-(beta)gal) induced a Th1 immune response (predominance of IgG2a antibodies, high frequency of IFN-gamma producing T cells) and large numbers of cytotoxic T lymphocytes. Prophylactic vaccination with AdCMV-(beta)gal abolished the production of specific IgE following subsequent immunization with (beta)gal-protein, and skewed the Th2-biased immune response to a Th1-orientated response. In contrast, therapeutic administration of AdCMV-(beta)gal after priming with (beta)gal-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.
Sudowe
S
S
Clinical Research Unit Allergology, Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
Montermann
E
E
Steitz
J
J
Tüting
T
T
Knop
J
J
Reske-Kunz
A B
AB
D000256:Adenoviridae / Q000235:genetics*; D000485:Allergens / Q000235:genetics* / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use*; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D007114:Immunization / Q000379:methods; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000485:Allergens; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D007371:Interferon-gamma; D001616:beta-Galactosidase