Suppression of the anti‐hapten IgE antibody response with hapten‐modified spleen cells

Weber, Ernst; Blaser, Kurt

doi:10.1002/eji.1830161210

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…168 More recently, Ag-SP were found to induce antigen-specific tolerance in mouse models of allergic airway inflammation and food allergy. 155 In both models, prophylactic treatment with Ag-SP inhibited development of Ag-specific IgE and inhibited eosinophilia and Th2 cytokine responses following acute antigen challenge.…”

Section: Adjuvants/delivery Vehiclesmentioning

confidence: 99%

Antigen-Specific Tolerance in Immunotherapy of Th2-Associated Allergic Diseases

2013

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Allergic diseases are an increasing health concern, particularly in the developed world. The standard clinical approach to treatment of allergic disease focuses on allergen avoidance and symptom control but does little to address the underlying Th2 bias of disease. Specific immunotherapy (SIT) consisting of controlled administration of allergen, however, has been demonstrated to successfully induce desensitization and tolerance in an antigen-specific manner for a variety of Th2-mediated diseases. This review focuses on the mechanisms by which current SIT approaches induce tolerance as well as discussing attempts to modify the safety and efficacy of SIT. These refinements focus on three major aspects of SIT: the route of antigen administration, modification of the antigen to remove allergenic epitopes and reduce adverse events and choice of adjuvant used to induce tolerance and/or immune deviation from Th2 to Th1 and regulatory T cell (Treg) phenotypes. Synthesis of these recent developments in SIT provides considerable promise for more robust therapies with improved safety profiles to improve resolution of allergic disease and its associated costs.

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Section: Adjuvants/delivery Vehiclesmentioning

confidence: 99%

Antigen-Specific Tolerance in Immunotherapy of Th2-Associated Allergic Diseases

2013

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“…Ragweed AgE with an original molecular weight of 38,000 kD, which has been modified to high-molecular-weight polymers of 200,000–20,000,000 kD, has been shown to be less allergenic and retain immunogenicity [76]. Allergens chemically conjugated to APC in spleen cells have also demonstrated specific IgE-suppressive activity without affecting IgG in a study with mice [77]. …”

Section: Strategies For Bypassing Effector Cell Surface Ige Cross-linmentioning

confidence: 99%

Regulation of Specific Immune Responses by Chemical and Structural Modifications of Allergens

Akdiş¹,

Blaser²

2000

Int Arch Allergy Immunol

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Specific immunotherapy (SIT) is an efficient treatment of allergic diseases to defined allergens. Despite being used in clinical practice since early in this century, more rational and safer regimens are required, because SIT is faced with the risk of anaphylaxis and standardization problems of allergen-extract-based treatments. A better understanding of the pathogenesis of allergy and of the mechanisms of SIT has led to various approaches to overcome these problems. Knowledge of the influence of IgE-facilitated antigen presentation on allergen-specific Th2 responses increased the efforts to generate non-IgE-binding allergens. The current principal approach to allergen modification is to modify B cell epitopes in order to prevent IgE binding and effector cell cross-linking while preserving T cell epitopes to retain the capacity of inducing tolerance. In this way, the modified allergen will be directed to T cells by a phagocytosis/pinocytosis-mediated antigen uptake mechanism, bypassing IgE cross-linking and IgE-dependent antigen presentation. Accordingly, a differential regulation of allergen-specific T cell cytokine patterns and IgE:IgG production was demonstrated by modifications of the three-dimensional structure of allergens because of linearity in T cell epitopes and conformation dependence in B cell epitopes. In this context, chemically modified allergen extracts with low IgE-binding capacity have been developed to reduce anaphylactic side effects since the early 1980s. The progress of recombinant techniques for producing allergens and allergen derivatives has led to a dramatic improvement in the ability of developing novel vaccines for the treatment of allergy. This has enabled mutation or deletion of decisive amino acids in B cell epitopes and fractionation or oligomerization of allergens by genetic engineering as fruitful approaches to generate hypoallergenic vaccines. Moreover, non-IgE-binding short T cell epitope peptides and single-amino-acid-altered peptide ligands represent potential candidates for future SIT.

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“…Previous studies have suggested that the reduced IgE binding of these allergoids could depend on the high molecular size of the modified molecules [19]. Experiments conducted in mice have confirmed reduced IgE interaction without affecting the induction of IgG responses [20]. High standard quality control is inevitable for therapeutics used in humans.…”

Section: Discussionmentioning

confidence: 99%

Detection of allergen composition and in vivo immunogenicity of depigmented allergoids of Betula alba

Carnés¹,

Himly

Gallego³

et al. 2009

Clin Experimental Allergy

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The mean protein content was 544+/-106 microg per mg of freeze-dried material for depigmented allergoids and 434+/-71 for native extracts. They retain the capacity to induce specific IgG antibodies against individual allergens present in the native extract. These findings confirm the immunogenicity of depigmented allergoids and may explain why patients treated with these vaccines are protected against the native allergens. Analysis of molecular size and allergen content may be useful techniques for characterization and standardization of allergoid products.

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Suppression of the anti‐hapten IgE antibody response with hapten‐modified spleen cells

Cited by 5 publications

References 39 publications

Antigen-Specific Tolerance in Immunotherapy of Th2-Associated Allergic Diseases

Antigen-Specific Tolerance in Immunotherapy of Th2-Associated Allergic Diseases

Regulation of Specific Immune Responses by Chemical and Structural Modifications of Allergens

Detection of allergen composition and in vivo immunogenicity of depigmented allergoids of Betula alba

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