A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi‐sensitivities

Wild, C.; Wallner, Michael; Hufnagl, Karin; Fuchs, H.; Hoffmann‐Sommergruber, Karin; Breiteneder, Heimo; Scheiner, Otto; Ferreira, Fátima; Wiedermann, Ursula

doi:10.1111/j.1398-9995.2006.01245.x

Cited by 24 publications

(31 citation statements)

References 39 publications

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“…Dominant T cell epitopes of different allergens and in different combinations have been investigated for intranasal application, resulting in reduction of allergen-specific IgE and IgG responses. However, allergen-specific isotypes are not completely eliminated and only short-term follow up was reported in these models (Hufnagl et al 2005(Hufnagl et al , 2008Marazuela et al 2008;Wild et al 2007). Involvement of Tregs and a Th2 to Th1 shift are important mechanisms in these protocols (Hufnagl et al 2008;Marazuela et al 2008;Winkler et al 2006).…”

Section: Induction Of Tolerance Via the Mucosal Routementioning

confidence: 93%

Cell-Based Therapy in Allergy

Baranyi

Gattringer

Valenta

et al. 2011

Vaccines Against Allergies

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IgE-mediated allergy is an immunological disorder occurring in response to otherwise harmless environmental antigens (i.e., allergens). Development of effective therapeutic or preventive approaches inducing robust tolerance toward allergens remains an unmet goal. Several experimental tolerance approaches have been described. The therapeutic use of regulatory T cells (Tregs) and the establishment of molecular chimerism are two cell-based strategies that are of particular interest. Treg therapy is close to clinical application, but its efficacy remains to be fully defined. Recent proof-of-concept studies demonstrated that transplantation of syngeneic hematopoietic stem cells modified in vitro to express a major allergen leads to molecular chimerism and robust allergen-specific tolerance. Here we review cell-based tolerance strategies in allergy, discussing their potentials and limitations.

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Section: Induction Of Tolerance Via the Mucosal Routementioning

confidence: 93%

Cell-Based Therapy in Allergy

Baranyi

Gattringer

Valenta

et al. 2011

Vaccines Against Allergies

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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%

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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“…To date, allergen immunotherapy is the only treatment that provides long-term clinical benefits. Novel strategies for development of allergen vaccines include the generation of low-affinity IgE-binding molecules Wild et al 2007). Therefore, allergens structural determination is a crucial step for the understanding of the molecular interactions between the allergen cells of the immune system, the development of allergen therapeutics and the biological function of the protein in the pollen.…”

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confidence: 99%

Sequence-specific 1H, 15N and 13C resonance assignments of Art v 1: a proline-rich allergen of Artemisia vulgaris pollen

et al. 2009

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Art v 1 is the major allergen of Artemisia vulgaris. The IgE raised against Art v 1 not only can cross-react with other proteins from the Asteraceae family members but also with components of various forms of food. Art v 1 is an important target for immunotherapy strategies, including vaccination with hypoallergenic derivatives or chimeras. We report the (1)H, (13)C, and (15)N resonance assignments of the recombinant Art v 1 and identification of secondary structures based on (13)C chemical shifts.

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A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi‐sensitivities

Abstract: The data indicate that such allergen chimers harboring several unrelated allergens or allergen peptides could serve as mucosal polyvalent vaccines for prevention of multi-sensitivities.

Cited by 24 publications

References 39 publications

Cell-Based Therapy in Allergy

Cell-Based Therapy in Allergy

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

Sequence-specific 1H, 15N and 13C resonance assignments of Art v 1: a proline-rich allergen of Artemisia vulgaris pollen

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