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.
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.
Hochreiter
Romana
R
Institute of Chemistry and Biochemistry, University of Salzburg, Austria.
Stepanoska
Tatjana
T
Ferreira
Fatima
F
Valenta
Rudolf
R
Vrtala
Susanne
S
Thalhamer
Josef
J
Hartl
Arnulf
A
D000485:Allergens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D015549:Basophil Degranulation Test; D018076:DNA, Complementary / Q000235:genetics; D018744:DNA, Plant / Q000235:genetics; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000628:therapy; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011058:Pollen; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014197:Trees; D019444:Vaccines, DNA / Q000627:therapeutic use*
D000485:Allergens; D052179:Antigens, Plant; D018076:DNA, Complementary; D018744:DNA, Plant; D010940:Plant Proteins; D019444:Vaccines, DNA; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E; D007371:Interferon-gamma