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Forschungsdatenbank PMU-SQQUID

A mimotope gene encoding the major IgE epitope of allergen Phl p 5 for epitope-specific immunization.
Wallmann, J; Proell, M; Stepanoska, T; Hantusch, B; Pali-Schöll, I; Thalhamer, T; Thalhamer, J; Jensen-Jarolim, E; Hartl, A;
Immunol Lett. 2009; 122(1):68-75
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Hartl Arnulf Josef

Abstract

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


Find related publications in this database (Keywords)

Allergy
DNA vaccine
Mimotope