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Forschungsdatenbank PMU-SQQUID

Prevention of allergen-specific IgE production and suppression of an established Th2-type response by immunization with DNA encoding hypoallergenic allergen derivatives of Bet v 1, the major birch-pollen allergen.
Hochreiter, R; Stepanoska, T; Ferreira, F; Valenta, R; Vrtala, S; Thalhamer, J; Hartl, A;
EUR J IMMUNOL. 2003; 33(6): 1667-1676.
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Hartl Arnulf Josef

Abstract


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*


Find related publications in this database (Keywords)

allergy
DNA-vaccination
Th1/Th2 cell
cytokine