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* Division of Immunopathology, Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria;
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Vienna General Hospital, Medical University of Vienna, Vienna, Austria;
Division of Structural Biology, Institute of Chemistry, Karl Franzens University of Graz, Graz, Austria; and
Institute of Medical Physics and Biophysics, University of Muenster, Muenster, Germany
The recognition of conformational epitopes on respiratory allergens by IgE Abs is a key event in allergic inflammation. We report a molecular strategy for the conversion of allergens into vaccines with reduced allergenic activity, which is based on the reassembly of non-IgE-reactive fragments in the form of mosaic proteins. This evolution process is exemplified for timothy grass pollen-derived Phl p 2, a major allergen for more than 200 million allergic patients. In a first step, the allergen was disrupted into peptide fragments lacking IgE reactivity. cDNAs coding for these peptides were reassembled in altered order and expressed as a recombinant mosaic molecule. The mosaic molecule had lost the three-dimensional structure, the IgE reactivity, and allergenic activity of the wild-type allergen, but it induced high levels of allergen-specific IgG Abs upon immunization. These IgG Abs crossreacted with group 2 allergens from other grass species and inhibited allergic patients’ IgE binding to the wild-type allergen. The mosaic strategy is a general strategy for the reduction of allergenic activity of protein allergens and can be used to convert harmful allergens into safe vaccines.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by grants F1805, F1809, and F1815 of the Austrian Science Fund, by a research grant from Biomay (Vienna, Austria), and by the Christian Doppler Research Association (Vienna, Austria).
2 Current address: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
3 Current address: Department of Hygiene, Microbiology, and Tropical Medicine, Hospital of the Elisabethinen, Linz, Austria.
4 Address correspondence and reprint requests to Dr. Rudolf Valenta, Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail address: rudolf.valenta{at}meduniwien.ac.at
5 Abbreviations used in this paper: SIT, allergen-specific immunotherapy; CD, circular dichroism; MFI, mean fluorescence intensity; nm, nanometers.
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  S. Padavattan, S. Flicker, T. Schirmer, C. Madritsch, S. Randow, G. Reese, S. Vieths, C. Lupinek, C. Ebner, R. Valenta, et al. High-Affinity IgE Recognition of a Conformational Epitope of the Major Respiratory Allergen Phl p 2 As Revealed by X-Ray Crystallography J. Immunol., February 15, 2009; 182(4): 2141 - 2151. [Abstract] [Full Text] [PDF]
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