PMU-Autor/inn/en
Hartl Arnulf JosefAbstract
A gene vaccine based on a mammalian expression vector containing the sequence of a peptide minnotope of Phi p 5 was constructed. To test whether mimotope gene vaccines can induce allergen-specific antibody responses via molecular mimicry, BALB/c mice were immunized using the minnotope construct with or without a tetanus toxin T-helper epitope. Moreover, intradermal injection was compared to epidermal application via gene gun immunization. Immunization with both mimotope gene constructs elicited allergen-specific antibody responses. As expected, gene gun bombardment induced a Th2-biased immune response, typically associated with IgG1 and IgE antibody production. In contrast, intradermal injection of the vaccine triggered IgG2a antibody expression without any detectable IgE levels, thus biasing the immune response towards Th1. In an RBL assay, mimotope-specific IgG antibodies were able to prevent cross-linking of allergen-specific IgE by Phl p 5. A construct coding for the complete Phi p 5 induced T-cell activation, IFN-gamma and IL-4 production. In contrast, the mimotope-DNA construct being devoid of allergen-specific T-cell epitopes had no capacity to activate allergen-specific T cells. Taken together, our data show that it is feasible to induce blocking IgG antibodies with a mimotope-DNA construct when applied intradermally. Thus the mimotope-DNA strategy has two advantages: (1) the avoidance of IgE induction and (2) the avoidance of triggering allergen-specific T-lymphocytes. We therefore suggest that minnotope gene vaccines are potential candidates for epitope-specific immunotherapy of type I allergy. (C) 2009 Published by Elsevier B.V.
Useful keywords (using NLM MeSH Indexing)
Animals
Basophils/cytology
Basophils/immunology
Basophils/metabolism*
Binding Sites, Antibody/genetics
Binding Sites, Antibody/immunology*
Biomimetic Materials
Cell Degranulation/genetics
Cell Degranulation/immunology
Cell Line, Tumor
Desensitization, Immunologic
Female
Genetic Engineering
Genetic Therapy
Immunodominant Epitopes/genetics*
Immunodominant Epitopes/immunology
Immunoglobulin E/immunology*
Immunoglobulin E/metabolism
Immunoglobulin G/blood
Interferon-gamma/secretion
Lymphocyte Activation/genetics
Lymphocyte Activation/immunology
Mice
Mice, Inbred BALB C
Phleum/genetics
Phleum/immunology*
Plant Proteins/adverse effects
Plant Proteins/genetics
Plant Proteins/immunology*
Plant Proteins/pharmacology
Pollen
Rats
Rhinitis, Allergic, Seasonal/immunology*
Rhinitis, Allergic, Seasonal/therapy
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Allergy