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Westritschnig, K; Linhart, B; Focke-Tejkl, M; Pavkov, T; Keller, W; Ball, T; Mari, A; Hartl, A; Stöcklinger, A; Scheiblhofer, S; Thalhamer, J; Ferreira, F; Vieths, S; Vogel, L; Böhm, A; Valent, P; Valenta, R.
A hypoallergenic vaccine obtained by tail-to-head restructuring of timothy grass pollen profilin, Phl p 12, for the treatment of cross-sensitization to profilin.
J Immunol. 2007; 179(11):7624-7634 Doi: 10.4049/jimmunol.179.11.7624 [OPEN ACCESS]
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Co-authors Med Uni Graz: Ball Tanja
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Abstract:: Profilins are highly cross-reactive allergens in pollens and plant food. In a paradigmatic approach, the cDNA coding for timothy grass pollen profilin, Phl p 12, was used as a template to develop a new strategy for engineering an allergy vaccine with low IgE reactivity. Non-IgE-reactive fragments of Phl p 12 were identified by synthetic peptide chemistry and restructured (rs) as a new molecule, Phl p 12-rs. It comprised the C terminus of Phl p 12 at its N terminus and the Phl p 12 N terminus at its C terminus. Phl p 12-rs was expressed in Escherichia coli and purified to homogeneity. Determination of secondary structure by circular dichroism indicated that the restructuring process had reduced the IgE-reactive alpha-helical contents of the protein but retained its beta-sheet conformation. Phl p 12-rs exhibited reduced IgE binding capacity and allergenic activity but preserved T cell reactivity in allergic patients. IgG Abs induced by immunization of mice and rabbits with Phl p 12-rs cross-reacted with pollen and food-derived profilins. Recombinant Phl p 12-rs, rPhl p 12-rs, induced less reaginic IgE to the wild-type allergen than rPhl p 12. However, the rPhl p 12-rs-induced IgGs inhibited allergic patients' IgE Ab binding to profilins to a similar degree as those induced by immunization with the wild type. Phl p 12-rs specific IgG inhibited profilin-induced basophil degranulation. In conclusion, a restructured recombinant vaccine was developed for the treatment of profilin-allergic patients. The strategy of tail-to-head reassembly of hypoallergenic allergen fragments within one molecule represents a generally applicable strategy for the generation of allergy vaccines.
Find related publications in this database (using NLM MeSH Indexing): Allergens - chemistry Allergens - genetics Allergens - immunology; Anti-Allergic Agents - chemistry Anti-Allergic Agents - immunology; Antibodies - chemistry Antibodies - genetics Antibodies - immunology; Antibody Specificity - genetics Antibody Specificity - immunology; Antigen-Antibody Reactions -; Antigens, Plant - chemistry Antigens, Plant - genetics Antigens, Plant - immunology; Binding Sites -; Circular Dichroism -; Epitopes - immunology; Genetic Engineering - methods; Histamine - immunology; Humans -; Immunoglobulin E - blood Immunoglobulin E - immunology; Immunoglobulin G - blood Immunoglobulin G - immunology; Models, Molecular -; Pollen - chemistry Pollen - genetics Pollen - immunology; Polymerase Chain Reaction -; Profilins - chemistry Profilins - genetics Profilins - immunology; Protein Structure, Secondary -; Recombinant Fusion Proteins - chemistry Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology; Sensitivity and Specificity -; T-Lymphocytes - immunology; Vaccines - chemistry Vaccines - genetics Vaccines - immunology