Variants of the timothy grass allergen Phl p 5b: new concept for a more efficient immunotherapy

Schramm, Gabriele; Kahlert, Helga; Suck, Roland; Weber, Bernhard H. F.; Stüwe, Hans-Thomas; Müller, Wolf‐Dieter; Bufe, Albrecht; Schlaak, M; Jäger, Lothar; Cromwell, Oliver; Fiebig, Helmut; Becker, W.M.

doi:10.1016/s0335-7457(99)80083-5

Cited by 2 publications

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“…These modified proteins bind minimal IgE Abs from peanut-allergic patients, although they promote T-cell proliferation to a similar extent as native peanut allergens. Similar results were obtained for the major birch pollen allergen Bet v 1 and the timothy grass pollen allergen Phl p 5b [43,44].…”

Section: Manipulation Of the Allergenic Properties Of Allergenssupporting

confidence: 82%

Requirements for effective IgE cross‐linking on mast cells and basophils

Knol¹

2006

Molecular Nutrition Food Res

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This article reviews the characteristics of high affinity IgE receptors (FcepsilonRI) and their role in the response to allergenic proteins. The requirements for successful cross-linking of FcepsilonRI on basophils and mast cells and subsequent degranulation by allergenic proteins will be explained in detail. Methods for in vitro analysis of allergen-induced mast cell and basophil degranulation will be described and issues/problems in applying these methods will be discussed. Finally, implications for manipulation of protein allergens will be discussed.

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Section: Manipulation Of the Allergenic Properties Of Allergenssupporting

confidence: 82%

Requirements for effective IgE cross‐linking on mast cells and basophils

Knol¹

2006

Molecular Nutrition Food Res

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“…In vitro experiments, studies in experimental animal models, and a recent clinical trial performed with recombinant grass pollen allergens indicate that four major grass pollen allergens (i.e., Phl p 1, Phl p 2, Phl p 5, and Phl p 6 from timothy grass pollen) comprise most of the relevant epitopes needed for the diagnosis and treatment of grass pollen allergy (24). Hypoallergenic derivatives for Phl p 1 (B cell peptides) (27) and Phl p 5 (deletion variants) (28) have been characterized but are not yet available for Phl p 6. Phl p 6 represents an 11.8-kDa, ␣ helical protein located on the polysaccharide-rich wall precursor bodies (P-particles) of timothy grass pollen (29).…”

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confidence: 99%

Genetic Engineering of the Major Timothy Grass Pollen Allergen, Phl p 6, to Reduce Allergenic Activity and Preserve Immunogenicity

Vrtala

Focke

Kopec

et al. 2007

The Journal of Immunology

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On the basis of IgE epitope mapping data, we have produced three allergen fragments comprising aa 1–33, 1–57, and 31–110 of the major timothy grass pollen allergen Phl p 6 aa 1–110 by expression in Escherichia coli and chemical synthesis. Circular dichroism analysis showed that the purified fragments lack the typical α-helical fold of the complete allergen. Superposition of the sequences of the fragments onto the three-dimensional allergen structure indicated that the removal of only one of the four helices had led to the destabilization of the α helical structure of Phl p 6. The lack of structural fold was accompanied by a strong reduction of IgE reactivity and allergenic activity of the three fragments as determined by basophil histamine release in allergic patients. Each of the three Phl p 6 fragments adsorbed to CFA induced Phl p 6-specific IgG Abs in rabbits. However, immunization of mice with fragments adsorbed to an adjuvant allowed for human use (AluGel-S) showed that only the Phl p 6 aa 31–110 induced Phl p 6-specific IgG Abs. Anti-Phl p 6 IgG Abs induced by vaccination with Phl p 6 aa 31–110 inhibited patients’ IgE reactivity to the wild-type allergen as well as Phl p 6-induced basophil degranulation. Our results are of importance for the design of hypoallergenic allergy vaccines. They show that it has to be demonstrated that the hypoallergenic derivative induces a robust IgG response in a formulation that can be used in allergic patients.

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Variants of the timothy grass allergen Phl p 5b: new concept for a more efficient immunotherapy

Cited by 2 publications

References 4 publications

Requirements for effective IgE cross‐linking on mast cells and basophils

Requirements for effective IgE cross‐linking on mast cells and basophils

Genetic Engineering of the Major Timothy Grass Pollen Allergen, Phl p 6, to Reduce Allergenic Activity and Preserve Immunogenicity

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