Characterization of the protective and therapeutic efficiency of a DNA vaccine encoding the major birch pollen allergen Bet v 1a.
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.


OBJECTIVE
DNA immunization using the Bet v 1a gene was evaluated with respect to its prophylactic and therapeutic efficacy.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hartl
A
A
Institute of Chemistry and Biochemistry, University of Salzburg, Salzburg, Austria.
Hochreiter
R
R
Stepanoska
T
T
Ferreira
F
F
Thalhamer
J
J
D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D000818:Animals; D029662:Betula / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000517:prevention & control*; D007111:Immunity, Cellular / Q000502:physiology; D007074:Immunoglobulin G / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen / Q000009:adverse effects / Q000276:immunology; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000494:pharmacology*
D000485:Allergens; D007074:Immunoglobulin G; D019444:Vaccines, DNA