IgE Mimotopes of Birch Pollen Allergen Bet v 1 Induce Blocking IgG in Mice

Abstract

Background: The induction of nonanaphylactogenic ‘blocking’ IgG antibodies capable of inhibiting the IgE/allergen interaction represents a favorable therapeutic concept for type I allergy. However, IgG antibodies to allergens may block or enhance specific IgE binding, depending on the recognized epitope. Taking the major birch pollen allergen Bet v 1 as a model, we developed a strategy for the precise induction of IgG antibodies of a desired epitope specificity. Methods: Random phage display peptide libraries were applied to define peptide structures mimicking natural epitopes (mimotopes) of Bet v 1. Selections were performed with BIP 1, a murine monoclonal antibody known to enhance the IgE binding to Bet v 1, and with anti-Bet v 1 IgE purified from patients’ sera. The characterized Bet v 1 mimotopes were used to localize the corresponding epitope at the surface of Bet v 1 by a computer-aided mathematical approach based on the three-dimensional structure and the chemical character of the amino acids. The Bet v 1 mimotopes were further used to immunize BALB/c mice. The specificity of the induced antibodies was tested by immunoblotting and inhibition assays. Results: With the three-dimensional epitope search it became possible to localize a discontinuous IgE epitope on the surface of Bet v 1 in a substantial distance from the IgG epitope of the monoclonal antibody BIP 1. Moreover, we could demonstrate that phage displaying mimotopes are immunogenic vectors for the precise induction of epitope-specific IgG. Immunization with BIP 1 mimotopes induced IgG enhancing the IgE binding to Bet v 1, whereas immunization with IgE mimotopes resulted in IgG capable of blocking human IgE binding in vitro. Conclusion: Allergen mimotopes can be used for the induction of anti allergen IgG of desired specificity. We propose that mimotope immunotherapy based on IgE mimotopes generated by biopannings may represent a future concept for therapy of type I allergy.

Egg Allergy: Diagnosis and Immunotherapy

“…Allergenic activity is reduced, inducing tolerance and Th1 responses [163,166,196,197] Recombinant allergens and recombinant hypoallergens Allergen specificity; induces blocking of antibodies and increases safety Immunomodulation occurs with the induction of T-cell tolerance [160,198,199] T cell peptides Induction of T-cell tolerance increases allergen specificity and increases safety [200][201][202] B cell peptides Induction of blocking antibodies increases allergen specificity and increases safety [150,186] Mimotopes Allergen specificity induces the blocking of antibodies in DNA vaccines [203][204][205] DNA Vaccines Induction of Th1 response leads to allergen specificity [150,206,207] Route/mode of administration Oral/sublingual administration Safety. The induction of T-cell anergy makes the treatment easy to perform and convenient for patients [208][209][210] Nasal administration Safe and convenient for patients [211,212] Adjuvant Al(OH) 3 Reduces anaphylactic side effects [213,214] CpG, MPL liposomes CpG reduces allergen activity Overall induces Th1 [215,216] Chitosan-nanoparticles Induction of T-cell tolerance [215,217] Carbohydrate based particles Ease of production and reduced tissue damage [206,218] Live vaccines Induces Th1 response [219][220][221] Surface layers Induces Th1 response [222,223] ...…”

From the allergen-recognition by antibodies to new therapeutic concepts

“…Im Zuge einer Immuntherapie mit natürlichen wie rekombinanten Allergenen können neben blockierenden jedoch auch anaphylaktogene IgG-Antikörper entstehen [51]. Wir gehen daher noch einen Schritt weiter und generieren Epitop-spezifische Vakzine.…”

A mimotope gene encoding the major IgE epitope of allergen Phl p 5 for epitope-specific immunization

“…The selected mimics resemble IgE binding epitopes of the allergen surface by virtue of their physico-chemical properties [1]. In peptide form, such epitope-mimics (mimotopes) have repeatedly been shown to induce epitope-specific, allergen-specific immune responses [2][3][4][5][6]. Due to the fact that mimotopes do not contain allergen-specific T-cell epitopes, the immune responses towards mimotopes depend on the recruitment of bystander Th-cells.…”

“…Therefore, they are able to prevent the high-affinity interaction between allergen and specific IgE antibodies [3,8] and thus can be called blocking antibodies [9,10]. In several studies we and others have already characterized peptides and anti-idiotypic Fab fragments being mimotopes of different allergens and antigens [2,6,[11][12][13].…”