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A Combination Vaccine for Allergy and Rhinovirus Infections Based on Rhinovirus-Derived Surface Protein VP1 and a Nonallergenic Peptide of the Major Timothy Grass Pollen Allergen Phl p 1¹

Johanna Edlmayr^*, Katarzyna Niespodziana^*, Birgit Linhart^*, Margarete Focke-Tejkl^*, Kerstin Westritschnig^*, Sandra Scheiblhofer, Angelika Stoecklinger, Michael Kneidinger, Peter Valent, Raffaela Campana^*, Josef Thalhamer, Theresia Popow-Kraupp and Rudolf Valenta^2,*

^* Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Department of Internal Medicine I, Division of Hematology and Hemostaseology, Department of Virology, Medical University of Vienna, Vienna, Austria; and Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria

Allergens and rhinovirus infections are among the most common elicitors of respiratory diseases. We report the construction of a recombinant combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived VP1, the surface protein which is critically involved in infection of respiratory cells, and a nonallergenic peptide of the major grass pollen allergen Phl p 1. Recombinant hybrid molecules consisting of VP1 and a Phl p 1-derived peptide of 31 aa were expressed in Escherichia coli. The hybrid molecules did not react with IgE Abs from grass pollen allergic patients and lacked allergenic activity when exposed to basophils from allergic patients. Upon immunization of mice and rabbits, the hybrids did not sensitize against Phl p 1 but induced protective IgG Abs that cross-reacted with group 1 allergens from different grass species and blocked allergic patients’ IgE reactivity to Phl p 1 as well as Phl p 1-induced basophil degranulation. Moreover, hybrid-induced IgG Abs inhibited rhinovirus infection of cultured human epithelial cells. The principle of fusing nonallergenic allergen-derived peptides onto viral carrier proteins may be used for the engineering of safe allergy vaccines which also protect against viral infections.

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 L214-B13, F1815, and DK-IAI of the Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) and in part by the Christian Doppler Research Foundation.

² Address correspondence and reprint requests to Dr. Rudolf Valenta, Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Medical University of Vienna, AKH Ebene 3Q, Währinger Gürtel 18-20, 1090 Vienna, Austria. E-mail address: rudolf.valenta{at}meduniwien.ac.at

³ Abbreviations used in this paper: HRV, human rhinovirus; KLH, keyhole limpet hemocyanin; HSA, human serum albumin; MFI, mean fluorescence intensity; SI, stimulation index; TCID₅₀, 50% tissue culture infectious dose; RBL, rat basophil leukemia cell.

⁴ The online version of this article contains supplemental material.