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SHR Neuro Cancer Cardio Lipid Metab Microb

Vrtala, S; Focke, M; Kopec, J; Verdino, P; Hartl, A; Sperr, WR; Fedorov, AA; Ball, T; Almo, S; Valent, P; Thalhamer, J; Keller, W; Valenta, R.
Genetic engineering of the major timothy grass pollen allergen, Phl p 6, to reduce allergenic activity and preserve immunogenicity.
J Immunol. 2007; 179(3):1730-1739 Doi: 10.4049/jimmunol.179.3.1730 [OPEN ACCESS]
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Co-authors Med Uni Graz: Ball Tanja
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Abstract:: 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 alpha-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 alpha 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.
Find related publications in this database (using NLM MeSH Indexing): Allergens - administration and dosage Allergens - biosynthesis Allergens - genetics Allergens - immunology; Animals -; Down-Regulation - genetics Down-Regulation - immunology; Female -; Gene Expression Regulation - immunology; Humans -; Immune Sera - biosynthesis; Immunoglobulin E - metabolism; Immunoglobulin G - biosynthesis Immunoglobulin G - metabolism; Mice -; Mice, Inbred BALB C -; Peptide Fragments - administration and dosage Peptide Fragments - chemical synthesis Peptide Fragments - genetics Peptide Fragments - immunology; Phleum - genetics Phleum - immunology; Plant Proteins - administration and dosage Plant Proteins - chemical synthesis Plant Proteins - genetics Plant Proteins - immunology; Pollen - genetics Pollen - immunology; Protein Engineering - methods; Protein Folding -; Protein Structure, Secondary -; Rabbits -; Recombinant Fusion Proteins - administration and dosage Recombinant Fusion Proteins - chemical synthesis Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology; Vaccines - administration and dosage Vaccines - chemical synthesis Vaccines - genetics Vaccines - immunology