Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom☆☆☆★★★

Müller, Ulrich; Akdiş, Cezmi A.; Fricker, Michael; Akdiş, Mübeccel; Blesken, Thorsten; Bettens, Florence; Blaser, Kurt

doi:10.1016/s0091-6749(98)70402-6

Cited by 413 publications

(303 citation statements)

References 39 publications

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“…Specific immunotherapy with whole allergen could induce unwanted anaphylactic reactions in patients, as indicated by increasing serum antigen-specific IgE levels during the desensitization process; 23,24 however, this phenomenon was not observed in our study, and oral feeding with total protein extracted from TG plants suppressed the Der p2-specific IgE levels in serum. In addition, a previous study found that long-term subcutaneous specific immunotherapy with native allergens Der p1 and Der p2 decreased serum specific IgE and asthma symptoms in patients.…”

Section: Discussioncontrasting

confidence: 75%

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

et al. 2011

Cell Mol Immunol

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In clinical therapy, the amount of antigen administered to achieve oral tolerance for allergic diseases is large, and the cost is a major consideration. In this study, we used tobacco plants to develop a large-scale protein production system for allergen-specific immunotherapy, and we investigated the mechanisms of oral tolerance induced by a transgenic plant-derived antigen. We used plants (tobacco leaves) transgenic for the Dermatophagoides pteronyssinus 2 (Der p2) antigen to produce Der p2. Mice received total protein extract from Der p2 orally once per day over 6 days (days 0-2 and days 6-8). Mice were also sensitized and challenged with yeast-derived recombinant Der p2 (rDer p2), after which the mice were examined for airway hyper-responsiveness and airway inflammation. After sensitization and challenge with rDer p2, mice that were fed with total protein extracted from transgenic plants showed decreases in serum Der p2-specific IgE and IgG1 titers, decreased IL-5 and eotaxin levels in bronchial alveolar lavage fluid, and eosinophil infiltration in the airway. In addition, hyper-responsiveness was also decreased in mice that were fed with total protein extracted from transgenic plants, and CD4 1 CD25 1 Foxp3 1 regulatory T cells were significantly increased in mediastinal and mesenteric lymph nodes. Furthermore, splenocytes isolated from transgenic plant protein-fed mice exhibited decreased proliferation and increased IL-10 secretion after stimulation with rDer p2. The data here suggest that allergen-expressing transgenic plants could be used for therapeutic purposes for allergic diseases.

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Section: Discussioncontrasting

confidence: 75%

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

et al. 2011

Cell Mol Immunol

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“…Because beneficial effects of immunotherapy are observed after treatment with relative high doses of allergen, the availability of the Ag, including the dose and t 1/2 of the Ag, the number of Ag-MHC complexes on the APC, and the affinity for the MHC and TCR have been suggested to play an important role in the efficacy of immunotherapy (13)(14)(15)(16).…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies suggested that immunotherapy exerted its beneficial effect by anergy induction of allergen-specific Th2 cells, or by modulation of the Th2 response toward a Th1 or a regulatory T cell response (11)(12)(13). These observations resulted in various hypotheses on the mechanism of allergen immunotherapy encompassing roles for the dose of Ag (including t 1/2 and number of ligands expressed on the APC), the affinity of the TCR for the MHC-peptide complex, the type of APC (differences in costimulatory molecules and cytokines), and the route of administration (10, 14 -16).…”

Section: The Efficacy Of Immunotherapy In An Experimentalmentioning

confidence: 99%

The Efficacy of Immunotherapy in an Experimental Murine Model of Allergic Asthma Is Related to the Strength and Site of T Cell Activation During Immunotherapy

Janssen

Oosterhout

Nijkamp

et al. 2000

The Journal of Immunology

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In the present study, the relation between the efficacy of immunotherapy, and the strength and site of T cell activation during immunotherapy was evaluated. We used a model of allergic asthma in which OVA-sensitized and OVA-challenged mice display increased airway hyperresponsiveness, airway inflammation, and Th2 cytokine production by OVA-specific T cells. In this model, different immunotherapy strategies, including different routes of administration, or treatment with entire OVA or the immunodominant T cell epitope OVA323–339, or treatment with a peptide analogue of OVA323–339 with altered T cell activation capacity were studied. To gain more insight in how immunotherapy affects allergen-specific T cells, the site of Ag-specific T cell activation and the magnitude of the T cell response induced during different immunotherapy strategies were determined using an adoptive transfer model. Our data suggest that amelioration of airway hyperresponsiveness and inflammation is associated with the induction of a strong, synchronized, and systemic T cell response, resulting in a decreased OVA-specific Th2 response. In contrast, deterioration of the disease after immunotherapy is associated with the induction of a weak nonsynchronized T cell response, resulting in the enhancement of the OVA-specific Th2 response after challenge.

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“…To date, clinical trials of peptide immunotherapy (PIT) have been performed in cat and BV allergies [20,22]. These studies showed modulation of the immune response against the whole allergen, inducing specific T cell tolerance and a decrease in the specific IgE/IgG4 ratio in BV-PIT.…”

Section: Discussionmentioning

confidence: 99%

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

Karamloo¹,

Schmid‐Grendelmeier

Kussebi³

et al. 2005

Eur. J. Immunol.

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Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A 2 (Api m 1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping amino acids were assembled in a different order in the Api m (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api m (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE FceRI cross-linking in sensitized individuals.

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Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom☆☆☆★★★

Cited by 413 publications

References 39 publications

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

The Efficacy of Immunotherapy in an Experimental Murine Model of Allergic Asthma Is Related to the Strength and Site of T Cell Activation During Immunotherapy

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

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