PMU-Autor/inn/en
Hartl Arnulf JosefAbstract
In atopic patients, programming towards a preferential Th2 immunity leads to IgE antibody production and cellular Th2 immunity against otherwise harmless antigens. We report the development of prophylactic and therapeutic DNA vaccines for the major birch-pollen allergen, Bet v 1. We constructed three DNA vaccines, coding for the complete cDNA, coding for two hypoallergenic fragments or coding for a hypoallergenic Bet v 1 mutant. The protective effect was studied in mice pretreated by intradermal DNA injections, then sensitized with Bet v 1 protein. Mice pretreated with any of the three Bet v 1-specific DNA vaccines were protected against allergic sensitization to Bet v 1. Protection was characterized by a lack of Bet v 1-specific IgE production, a lack of basophil activation and an enhanced IFN-gamma expression. DNA vaccines with wild-type Bet v 1 induced strong Bet v 1-specific antibody responses whereas DNA vaccines with hypoallergenic Bet v 1 derivatives induced no (fragments) or only transient (mutant) Bet v 1-specific antibody responses. A therapeutic approach with the fragment-DNA vaccine reduced IgE production and stimulated a sustained Th1 cytokine milieu. Our results demonstrate that DNA vaccines with hypoallergenic forms of the allergen specifically protect against sensitization and suppress established Th2-type responses. This concept may be applied for the development of safe and specific DNA vaccines for the prophylaxis and therapy of allergic diseases.
Useful keywords (using NLM MeSH Indexing)
Allergens/chemistry
Allergens/genetics
Allergens/immunology*
Animals
Antigens, Plant
Basophil Degranulation Test
DNA, Complementary/genetics
DNA, Plant/genetics
Female
Humans
Hypersensitivity, Immediate/immunology
Hypersensitivity, Immediate/therapy
Immunoglobulin E/biosynthesis*
Immunoglobulin E/immunology
Interferon-gamma/biosynthesis
Mice
Mice, Inbred BALB C
Plant Proteins/chemistry
Plant Proteins/genetics
Plant Proteins/immunology*
Pollen
Rhinitis, Allergic, Seasonal/immunology
Rhinitis, Allergic, Seasonal/therapy*
Th1 Cells/immunology
Th2 Cells/immunology*
Trees
Vaccines, DNA/therapeutic use*
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