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SHR Neuro Cancer Cardio Lipid Metab Microb
Ball, T; Linhart, B; Sonneck, K; Blatt, K; Herrmann, H; Valent, P; Stoecklinger, A; Lupinek, C; Thalhamer, J; Fedorov, AA; Almo, SC; Valenta, R.
Reducing allergenicity by altering allergen fold: a mosaic protein of Phl p 1 for allergy vaccination.
Allergy. 2009; 64(4):569-580
Doi: 10.1111/j.1398-9995.2008.01910.x
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- Ball Tanja
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- Abstract:
- BACKGROUND: The major timothy grass pollen allergen, Phl p 1, resembles the allergenic epitopes of natural group I grass pollen allergens and is recognized by more than 95% of grass-pollen-allergic patients. Our objective was the construction, purification and immunologic characterization of a genetically modified derivative of the major timothy grass pollen allergen, Phl p 1 for immunotherapy of grass pollen allergy. METHODS: A mosaic protein was generated by PCR-based re-assembly and expression of four cDNAs coding for Phl p 1 fragments and compared to the Phl p 1 wild-type by circular dichroism analysis, immunoglobulin E (IgE)-binding capacity, basophil activation assays and enzyme-linked immunosorbent assay competition assays. Immune responses to the derivative were studied in BALB/c mice. RESULTS: Grass-pollen-allergic patients exhibited greater than an 85% reduction in IgE reactivity to the mosaic as compared with the Phl p 1 allergen and basophil activation experiments confirmed the reduced allergenic activity of the mosaic. It also induced less Phl p 1-specific IgE antibodies than Phl p 1 upon immunization of mice. However, immunization of mice and rabbits with the mosaic induced IgG antibodies that inhibited patients' IgE-binding to the wild-type allergen and Phl p 1-induced degranulation of basophils. CONCLUSION: We have developed a strategy based on rational molecular reassembly to convert one of the clinically most relevant allergens into a hypoallergenic derivative for allergy vaccination.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Allergens - biosynthesis Allergens - chemistry Allergens - immunology
- Amino Acid Sequence -
- Animals -
- Basophils - immunology Basophils - secretion
- Desensitization, Immunologic - methods
- Epitopes, T-Lymphocyte - chemistry Epitopes, T-Lymphocyte - immunology
- Female -
- Histamine - biosynthesis Histamine - immunology
- Humans -
- Immunoglobulin E - blood Immunoglobulin E - immunology
- Immunoglobulin G - blood Immunoglobulin G - immunology
- Lymphocyte Activation - immunology
- Male -
- Mice -
- Mice, Inbred BALB C -
- Middle Aged -
- Molecular Sequence Data -
- Plant Proteins - biosynthesis Plant Proteins - chemistry Plant Proteins - immunology
- Polymerase Chain Reaction -
- Protein Structure, Quaternary -
- Rabbits -
- Rats -
- Recombinant Proteins - biosynthesis Recombinant Proteins - chemical synthesis Recombinant Proteins - immunology
- Rhinitis, Allergic, Seasonal - immunology Rhinitis, Allergic, Seasonal - prevention and control
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization -
- T-Lymphocytes - immunology
- Find related publications in this database (Keywords)
- allergens
- immunotherapy
- pollens