Clinical Evaluation of Genetically Engineered Hypoallergenic rBet v 1 Derivatives

Pauli, G.; Purohit, Ashok; Oster, J.P.; Blay, F. De; Vrtala, Susanne; Niederberger, Verena; Valenta, Rudolf

doi:10.1159/000024074

Cited by 10 publications

(8 citation statements)

References 4 publications

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“…molecules retaining the important structural features for the induction of T-cell-mediated immune responses but lacking the capability to bind IgE [70]. For various allergenic sources including birch and grass pollen allergens, as well as peanut and mite allergens, hypoallergenic variants have been genetically engineered, produced and partly evaluated in clinical studies [71, 72, 73, 74, 75, 76, 77, 78, 79, 80]. …”

Section: The Potential or Rallergens For Diagnostic Applicationmentioning

confidence: 99%

“…Many isoforms of Bet v 1 have been reported, some of them lacking the ability to bind IgE but retaining the full capability of stimulating T-cell proliferation [70]. These naturally occurring isoforms as well as genetically engineered variants lacking IgE-binding capability are considered as potential candidates for improvement of allergen-specific immunotherapy [71, 72, 73, 74, 75, 76]. Bet v 1 fragments as well as dimerized and trimerized molecules have been examined for their ability to elicit type I skin reactions in vivo delineating new possibilities for the generation of potentially safe vaccines by genetic engineering [61, 72, 76].…”

Section: The Potential or Rallergens For Diagnostic Applicationmentioning

confidence: 99%

“…Mostly due to restrictions by ethical and legal restrictions, skin tests have been performed only in a limited number of countries including Austria [60], Brazil [100], Canada [134], France [71, 76, 93], Singapore [101], Spain [84], Sweden [28, 72, 150, 151], Switzerland [46, 47, 61, 62, 63, 82, 103, 106, 107, 111, 116, 152, 153, 154], Taiwan [94, 155]and Venezuela [98, 99]. Authors from other nations, including the USA, have collected extensive data with recombinant allergens; however, the skin tests with the rAllergens had to be performed elsewhere.…”

Section: Ethical and Legal Aspectsmentioning

confidence: 99%

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Recombinant Allergens for Skin Testing

Schmid‐Grendelmeier¹,

Crameri²

2001

Int Arch Allergy Immunol

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Skin testing is a basic diagnostic procedure widely used to explore immediate-type reactions to allergen preparations in vivo. Despite their reliability, if standardized extracts are used, skin tests suffer from limited reproducibility due to difficulties in preparing consistently standardized extracts from natural raw material. Starting from allergen-encoding cDNAs, large amounts of highly pure allergens with a high batch-to-batch consistency satisfying the quality requirements of medicinal products manufactured by recombinant DNA technology can be produced. These reagents are expected to be qualitatively superior to the commercially available allergen preparations used for the in vitro and in vivo diagnosis of allergic conditions. In this article the current literature available on skin testing with such recombinant allergens (rAllergens) is reviewed and critically analyzed. To date many different rAllergens of various pollens, moulds, mites, bee venom, latex and celery have been used in skin testing in more than 1,600 allergic and control individuals. Skin prick tests as well as intradermal skin tests with rAllergens prove to be highly specific and safe. The diagnostic sensitivity of single rAllergens is generally lower than those obtained with allergen extracts, but can be considerably increased by using rAllergen panels covering the most important allergenic structures present in a given complex allergenic extract. Moreover, quantitative skin testing with single rAllergens allows interesting insights into correlations between the in vivo and in vitro sensitization to a given allergen. In conclusion, skin testing with rAllergens offers a highly specific and safe additional diagnostic tool to elucidate patient- and disease-specific sensitization patterns which will be needed for the development of patient-tailored immunotherapeutic treatments.

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Section: The Potential or Rallergens For Diagnostic Applicationmentioning

confidence: 99%

Section: The Potential or Rallergens For Diagnostic Applicationmentioning

confidence: 99%

Section: Ethical and Legal Aspectsmentioning

confidence: 99%

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Recombinant Allergens for Skin Testing

Schmid‐Grendelmeier¹,

Crameri²

2001

Int Arch Allergy Immunol

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“…Together, the fragments harbored all relevant T cell epitopes. Skin reactivity and histamine release were greatly reduced when compared to the native intact Bet v 1 allergen [65,66]. Further, immunization of mice and rabbits with Bet v 1 fragments induced IgG antibodies that inhibited binding of IgE from allergic patients to wild-type Bet v 1 [67].…”

Section: Allergen Fragmentsmentioning

confidence: 98%

“…When compared to the Bet v 1 monomer, the Bet v 1 trimer induced similar proliferation and cytokine production upon stimulation of Bet v 1-specific T cell clones. In vivo studies in animal models showed the ability of the Bet v 1 trimer to induce IgG blocking antibodies, which inhibited binding of human IgEs to rBet v 1 [65,66,70].…”

Section: Allergen Oligomersmentioning

confidence: 99%

Modified Recombinant Allergens for Safer Immunotherapy

Ferreira

Briza²,

Inführ³

et al. 2006

IADT

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Molecular cloning and recombinant production of allergens offered new perspectives for the increasing problem of allergies. A variety of preparations are being developed aiming to increase safety and improve efficacy of specific immunotherapy. Recombinant-based approaches are mostly focused on genetic modification of allergens to produce molecules with reduced allergenic activity and conserved antigenicity, i.e. hypoallergens. Studies dealing with genetic modifications of allergen genes reported the production of site-directed mutants, deletion mutants, allergen fragments and oligomers, and allergen chimeras. An alternative to genetic engineering is the chemical modification of pure recombinant allergens. It has been shown that allergens modified with immunostimulatory DNA sequences (allergen-ISS conjugates), which masks IgE epitopes and adds a desirable Th1-inducing character to the allergen molecule. Other chemical modifications include oligomerization by aldehydes (allergoids) and maleylation, which seems to target allergens to particular antigen presenting cells. Several of these modified allergen preparations have been already evaluated for their safety in clinical provocation studies. So far, clinical trials showed the efficacy and safety of immunotherapy with an Amb a 1-ISS conjugate for ragweed pollen-allergic patients. In addition, a preparation consisting of hypoallergenic fragments of Bet v 1 was evaluated for immunotherapy of birch pollen-allergic patients. In parallel, several animal studies have now demonstrated the potential of genetic immunization for allergy treatment in the future.

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Allergen mimotopes

Riemer

Scheiner

Jensen‐Jarolim

2004

Methods

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The causative treatment of type I allergies is a long pursued goal in immunology. To design safe and efficient vaccine preparations, the interaction of the allergen and the symptom-inducing IgE antibodies still needs to be better understood. In this article, we describe the use of the phage display technique in allergy. It yields epitope mimics, so-called mimotopes, which can be employed for both, investigation of allergen-IgE interactions and definition of safe novel vaccines.

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Clinical Evaluation of Genetically Engineered Hypoallergenic rBet v 1 Derivatives

Cited by 10 publications

References 4 publications

Recombinant Allergens for Skin Testing

Recombinant Allergens for Skin Testing

Modified Recombinant Allergens for Safer Immunotherapy

Allergen mimotopes

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