Engineering of major house dust mite allergens Der p 1 and Der p 2 for allergen‐specific immunotherapy

Asturias, Juan A.; Ibarrola, I.; Arilla, Maite; Vidal, Carmen; Ferrer, A.; Gamboa, P. M.; Viñuela, Juan E.; Sánz, M L; Andréu, Carmen; Martı́nez, Alberto

doi:10.1111/j.1365-2222.2009.03264.x

Cited by 63 publications

(43 citation statements)

References 53 publications

(77 reference statements)

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“…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%

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: Discussionmentioning

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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“…When multiple allergens are involved in patient sensitisation, a valid option is to create hybrid molecules assembling those allergens. This approach, which has previously been applied to grass and Parietaria pollens, bee and wasp venom allergens and more recently to mite [8,9,10,30,31,32], leads to the production of a single molecule, thus facilitating manufacturing and development, whilst establishing a fixed molar ratio between allergens. With the aim to develop a recombinant candidate vaccine against respiratory allergies associated with common HDM species, we applied this strategy to two major allergens from the D. pteronyssinus species, namely Der p 1 and Der p 2, in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Beyond evidence of cysteine engagement in intermolecular bridges, head to tail fusion of the two allergens in the absence of a flexible linker might cause stringent structural constraints on the two moieties precluding refolding. The characterization in parallel studies of other recombinant allergen hybrids yielded disparate results with respect to their folding properties secondary structure [8,9,10,30,31]. For example, a Parietaria judaica Par j 1-Par j 2 fusion protein exhibited a complete loss of secondary structure [30], whereas a refolded grass pollen-chimeric protein assembling Phl p 1, 2, 5 and 6 had a CD spectrum equivalent to the mixture of corresponding allergens [9].…”

Section: Discussionmentioning

confidence: 99%

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Recombinant Fusion Proteins Assembling Der p 1 and Der p 2 Allergens from <i>Dermatophagoides pteronyssinus</i>

Bussières

Floch²,

Bulder³

et al. 2010

Int Arch Allergy Immunol

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Background: Fusion proteins assembling multiple allergens can be engineered by recombinant DNA technologies in order to produce tools for diagnostic and immunotherapeutic purposes. Herein, we developed and characterized chimeras assembling Der p 1 and Der p 2 allergens as potential candidate vaccines against house dust mite allergy. Methods: Fusion proteins encompassing Der p 2 with either mature or proDer p 1 were expressed in Escherichia coli or Pichia pastoris. Forms with mutation in Der p 1 catalytic site were also engineered. Purified chimeras were characterized by immunoblotting, circular dichroism, disulfide bond mapping, basophil and T lymphocyte stimulation assays. Results: Four fusion proteins were expressed in E. coli as inclusion bodies, whereas only chimeras comprising proDer p 1 were obtained in yeast. All such hybrids formed polymers and aggregates, and yeast-expressed chimeras were unstable. Circular dichroism analysis performed after refolding of bacteria expressed chimeras encompassing mature Der p 1 confirmed partial folding, consistent with the occurrence of both correct and inappropriate intramolecular disulfide bonds. All fusion molecules were recognized by Der p 1- and Der p 2-specific human IgEs, monoclonal and polyclonal antibodies. Fusion proteins activate basophils from mite-allergic patients and trigger the proliferation of specific CD4+ T cells, albeit to a lower level when compared to individual allergens. Conclusions: Production of multiple Der p 1-Der p 2 fusion proteins exhibiting partial folding and proper antigenic properties has been achieved. Nonetheless, significant solubility and stability issues currently limit the application of such chimeras for immunotherapy or diagnostic.

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“…Allergen extract-based SIT includes the risk of anaphylactic side effects and the potential to induce novel sensitization to proteins from vaccines [102]. On the other hand, it might be difficult to standardize such vaccines leading to inconsistent results in SIT.…”

Section: Clinical Usementioning

confidence: 99%

Mechanisms of allergen-specific immunotherapy

2011

Journal of Allergy and Clinical Immunology

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Engineering of major house dust mite allergens Der p 1 and Der p 2 for allergen‐specific immunotherapy

Abstract: QM1 and QM2 hybrids exhibited less IgE-binding activity but preserved immunogenicity and fulfilled the basic requirements for hypoallergenic molecules suitable for a future SIT of HDM allergy.

Cited by 63 publications

References 53 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

Recombinant Fusion Proteins Assembling Der p 1 and Der p 2 Allergens from <i>Dermatophagoides pteronyssinus</i>

Mechanisms of allergen-specific immunotherapy

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