From Allergen Genes to Allergy Vaccines

Valenta, Rudolf; Ferreira, Fátima; Focke‐Tejkl, Margarete; Linhart, Birgit; Niederberger, Verena; Swoboda, Ines; Vrtala, Susanne

doi:10.1146/annurev-immunol-030409-101218

Cited by 197 publications

(181 citation statements)

References 231 publications

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“…Analysis of Der p1 revealed the presence of smaller fragments, sized 25 kDa (a), 17 kDa (b), and 14 kDa (c, Figure 1B). These fragments correspond to Der p1 breakdown products given the endogenous cysteine protease activity of Der p1 11, 12. Maldi‐TOF analysis on these fragments confirmed their identity as Der p1 peptides (Figure 1B).…”

Section: Resultsmentioning

confidence: 75%

“…Treatment options for HDM allergy include allergen avoidance and SIT 11. However, HDM extracts are variable in content of allergens,12, 13 and stability is limited 14. Given the fact that sensitization to Der p1 and 2 identifies more than 95% of HDM‐allergic individuals9, 13 and their causal role in early sensitization,10 SIT with purified Der p1 and 2 might be a more attractive therapeutic approach compared to the use of HDM extracts.…”

Section: Introductionmentioning

confidence: 99%

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Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Hesse

Ieperen

Habraken

et al. 2018

Allergy

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BackgroundAllergen‐specific immunotherapy can induce long‐term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β‐glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment.AimsHere, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM)‐driven mouse model of allergic asthma.Materials and methods HDM‐sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen‐induced ear swelling response (ESR), airway hyperresponsiveness (AHR), and inflammation in bronchoalveolar lavage fluid (BAL) and lung tissue.Results ESR measurement shows suppression of early allergic response in HDM‐SCIT– and DerP1/2‐SCIT–treated mice. Both HDM‐SCIT and DerP1/2‐SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2‐SCIT is able to significantly suppress type 2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2‐SCIT treatment is uniquely able suppress CCL20 and showed a trend toward suppression of IL‐33, CCL17 and eotaxin levels in lung tissue.DiscussionTaken together, these data show that purified DerP1/2‐SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDM‐induced activation of lung structural cells including airway epithelium.ConclusionsWe postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.

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Section: Resultsmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Hesse

Ieperen

Habraken

et al. 2018

Allergy

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“…The availability of the disease-causing allergens is not only important to study the mechanisms of wheat food allergy, but also to improve diagnosis and therapy (18). The structure of wheat allergens can be either identified by proteomic approaches (19) or by molecular cloning technologies (20).…”

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confidence: 99%

Molecular and Immunological Characterization of Tri a 36, a Low Molecular Weight Glutenin, as a Novel Major Wheat Food Allergen

Baar

Pahr

Constantin

et al. 2012

The Journal of Immunology

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Wheat is an essential element in our nutrition but one of the most important food allergen sources. Wheat allergic patients often suffer from severe gastrointestinal and systemic allergic reactions after wheat ingestion. In this study, we report the molecular and immunological characterization of a new major wheat food allergen, Tri a 36. The cDNA coding for a C-terminal fragment of Tri a 36 was isolated by screening a wheat seed cDNA expression library with serum IgE from wheat food-allergic patients. Tri a 36 is a 369-aa protein with a hydrophobic 25-aa N-terminal leader peptide. According to sequence comparison it belongs to the low m.w. glutenin subunits, which can be found in a variety of cereals. The mature allergen contains an N-terminal domain, a repetitive domain that is rich in glutamine and proline residues, and three C-terminal domains with eight cysteine residues contributing to intra- and intermolecular disulfide bonds. Recombinant Tri a 36 was expressed in Escherichia coli and purified as soluble protein. It reacted with IgE Abs of ∼80% of wheat food-allergic patients, showed IgE cross-reactivity with related allergens in rye, barley, oat, spelt, and rice, and induced specific and dose-dependent basophil activation. Even after extensive in vitro gastric and duodenal digestion, Tri a 36 released distinct IgE-reactive fragments and was highly resistant against boiling. Thus, recombinant Tri a 36 is a major wheat food allergen that can be used for the molecular diagnosis of, and for the development of specific immunotherapy strategies against, wheat food allergy.

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“…[18,20]. Studies using recombinant allergens and defined allergen epitopes for analysis, as well as SIT trials performed with purified recombinant allergens and recombinant hypoallergenic allergen derivatives, have confirmed that a major mechanism of SIT is the induction of allergen-specific IgG-blocking antibodies [14,25,36,37]. Moreover, it has been demonstrated that allergen-specific blocking IgG can also inhibit IgE-facilitated allergen presentation by antigen-presenting cells to T cells and thus suppress allergen-induced T-cell activation [13,38,39].…”

Section: Milestones In the Development Of Sitmentioning

confidence: 99%

“…Allergen sequences became available, avoiding the need for cumbersome purification of allergen components from natural allergen extracts. A new phase in the development of SIT began with the ability to produce synthetic peptides, pure recombinant allergens and hypoallergenic allergen derivatives for SIT [25]. With the aim of inducing T-cell tolerance, allergen-derived T-cell epitope-containing synthetic peptides were administered to allergic patients in immunotherapy trials approximately 10 years later [26].…”

Section: Milestones In the Development Of Sitmentioning

confidence: 99%

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

Valenta

Campana

Marth

et al. 2012

Journal of Internal Medicine

101

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Immunoglobulin E-mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life-threatening systemic anaphylaxis. At present, allergen-specific immunotherapy (SIT), which is based on the administration of the disease-causing allergens, is the only diseasemodifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well-defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen-specific strategies for prevention of allergic disease.

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From Allergen Genes to Allergy Vaccines

Cited by 197 publications

References 231 publications

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Molecular and Immunological Characterization of Tri a 36, a Low Molecular Weight Glutenin, as a Novel Major Wheat Food Allergen

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

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