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* Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, and
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria;
Institute of Chemistry/Structural Biology, Karl Franzens University Graz, Graz, Austria;
Institute of Physiology and Pathophysiology, Paracelsus Private Medical University Salzburg, and
¶ Department of Molecular Biology, Division of Allergy and Immunology, University of Salzburg, Salzburg, Austria; and
|| Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461
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 
-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 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.
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 work was supported by Christian Doppler Stiftung (Vienna, Austria), by a research grant from Biomay (Vienna, Austria), and by Austrian Science Fund Grants F01801, F01803, F01805, F01815, S8811, J1835, and J2122.
2 Address correspondence and reprint requests to Dr. Rudolf Valenta, Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail address: rudolf.valenta{at}meduniwien.ac.at
3 Abbreviations used in this paper: KLH, keyhole limpet hemocyanin; CD, circular dichroism.
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