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

Allergy. 2004 Jan;59(1):65-73. doi: 10.1046/j.1398-9995.2003.00335.x.

Abstract

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Allergens
  • Immunoglobulin G
  • Vaccines, DNA