PMU-Autor/inn/en
Hartl Arnulf JosefAbstract
BACKGROUND
An estimated 100 million individuals suffer from birch pollen allergy. More than 95% of birch pollen-allergic subjects react with the major birch pollen allergen Bet v 1a, and almost 60% of them are sensitized exclusively to this allergen.
DNA immunization using the Bet v 1a gene was evaluated with respect to its prophylactic and therapeutic efficacy.
A DNA vaccine containing the entire Bet v 1a cDNA under the control of a CMV-promoter was constructed. In order to estimate the protective efficiency, animals received three injections of this vaccine prior to sensitization with recombinant Bet v 1a. Vice versa, in a therapeutic approach, sensitization was followed by treatment with the DNA vaccine.
The Bet v 1a DNA vaccine induced strong Bet v 1-specific antibody responses with a Th1-biased response type. Animals which received the DNA vaccine were protected against a following allergic sensitization with Bet v 1a. The protective effect was characterized by suppression of Bet v 1-specific immunoglobulin (Ig)E production, lack of basophil activation and enhanced interferon (IFN)-gamma expression. In a therapeutic situation, treatment of sensitized animals with DNA vaccines decreased IgE production, IgE-mediated basophil release and drastically reduced anaphylactic activity as measured by passive cutaneous anaphylaxis assays. Concerning the cellular immune response, DNA immunization induced a sustaining and dominant shift from a Th2 type response towards a balanced Th1/Th2 type response as indicated by increased IFN-gamma but unchanged IL-5 levels in lymphoproliferation assays.
The results demonstrate the allergen-specific protective and therapeutic efficacy of a DNA vaccine encoding the clinically highly relevant allergen Bet v 1a indicating the suitability of this concept for the treatment of allergic diseases.
Useful keywords (using NLM MeSH Indexing)
Allergens/adverse effects
Allergens/immunology
Animals
Betula/immunology*
Desensitization, Immunologic/methods*
Disease Models, Animal
Female
Hypersensitivity/prevention*
control*
Immunity, Cellular/physiology
Immunoglobulin G/analysis
Mice
Mice, Inbred BALB C
Pollen/adverse effects
Pollen/immunology
Probability
Random Allocation
Reference Values
Sensitivity and Specificity
Statistics, Nonparametric
Vaccination/methods
Vaccines, DNA/pharmacology*
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