Hypoallergenic Der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy

Chen, Kuan Wei; Blatt, Katharina; Thomas, Wayne R.; Swoboda, Ines; Valent, Peter; Valenta, Rudolf; Vrtala, Susanne

doi:10.1016/j.jaci.2012.05.035

Cited by 84 publications

(61 citation statements)

References 34 publications

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“…This fusion peptide reduced T-cell activation in vitro and induced allergen-specific IgG in a rabbit model. Similar results were provided by Chen et al [49,50] (using carrier-bound Der p 2 peptides or rDer p 2/1 mosaic proteins).…”

Section: Key Pointssupporting

confidence: 88%

Novel immunotherapy vaccine development

Jutel

Akdiş

2014

Current Opinion in Allergy &Amp; Clinical Immunology

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PURPOSE OF REVIEW: Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept -as well as large, multicenter clinical studies. RECENT FINDINGS: The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. SUMMARY: The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients. Purpose of reviewAllergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-ofconcept -as well as large, multicenter clinical studies. Recent findingsThe most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. SummaryThe cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

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Section: Key Pointssupporting

confidence: 88%

Novel immunotherapy vaccine development

Jutel

Akdiş

2014

Current Opinion in Allergy &Amp; Clinical Immunology

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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%

“…Other approaches to develop novel therapeutic allergy vaccines for use in SIT for HDM include the generation of recombinant hypoallergenic combination vaccines of Der p1 and 2, which were shown to have limited IgE reactivity, while retaining its T‐cell epitopes and the ability to induce neutralizing antibody response in experimental models that could block IgE binding 11, 28. The use of these hypoallergenic recombinant vaccines holds the promise of inducing fewer side effects during therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Although hypoallergenic proteins are considered to have a better safety profile during treatment, is currently unknown whether hypoallergenic vaccines have a comparable therapeutic efficacy compared to IgE‐activating allergens. Initial studies show that hypoallergenic proteins can induce neutralizing antibodies that inhibit allergen‐mediated cross‐linking of IgE 11, 30. IgE cross‐linking vaccines might have some additional therapeutic efficacy due to so‐called piecemeal degranulation of mast cells and basophils, which is thought to contribute to protection against allergic responses especially during the early phase of treatment due to inactivation or exhaustion of these effector cells 30.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, early onset of sensitization to group 1, 2, or 23 allergens was associated with sensitization to more HDM allergens and with allergic rhinitis and asthma at school age, indicating the clinical relevance of these sensitization patterns 10. 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.…”

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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Allergen‐specific immunotherapy by recombinant Der P1 allergen‐derived peptide‐based vaccine in an allergic mouse model

Moghanloo

Forouzanfar

Jafarinia

et al. 2023

Immunity Inflam & Disease

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Aim: Increased IgE levels have made house dust mite allergens one of the most frequent causes of allergies worldwide. Treatment reduces the IgE antibodies and types two cytokines, namely interleukin-4 (IL-4) and IL-13.Although existing treatments significantly reduce IgE or IL-4/IL-13, they are very costly. This study aimed to construct a recombinant protein derived from rDer p1 peptides in the form of an immunotherapy approach and to measure the response of IgE and IgG antibodies.Methods: The proteins were isolated, purified, and evaluated using the SDS-PAGE and Bradford test and confirmed by using Western blot. To evaluate immunotherapy efficiency, 24 BALB/C mice were sensitized intraperitoneally with house dust mites (HDM) adsorbed to Aluminum hydroxide (Alum) and randomly divided into four groups of six: control sensitized, HDM extract, rDer p1, and DpTTDp vaccine. To immunization, four groups of random mice were each treated with phosphate-buffered saline, 100 μg of rDer p1 protein, DpTTDp, or HDM extract, every 3 days. Direct ELISA determined HDMspecific IgG and IgE subclasses. Data were analyzed in SPSS and Graph pad prism software. Values of p < .05 were considered significant.Results: After immunization of mice, the rDer P1 and recombinant vaccine like HDM extract increased IgG antibody titer and decreased IgE-dependent reactivity in allergic mice to rDer P1. Also, the levels of inflammatory IL-4 and IL-13 cytokines as allergic stimulants decreased. Conclusion:The use of present available recombinant proteins is considered a viable, cost-effective, and long-term option for providing effective HDM allergy immunotherapy vaccines without side effects.

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Hypoallergenic Der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy

Abstract: Background-More than 50% of allergic patients have house dust mite (HDM) allergy. Group 1 and 2 allergens are the major HDM allergens.

Cited by 84 publications

References 34 publications

Novel immunotherapy vaccine development

Novel immunotherapy vaccine development

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

Allergen‐specific immunotherapy by recombinant Der P1 allergen‐derived peptide‐based vaccine in an allergic mouse model

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