Reducing allergenicity by altering allergen fold: A mosaic protein of Phl p 1 for allergy vaccination

T. Ball, B. Linhart, K. Sonneck, K. Blatt, H. Herrmann, P. Valent, A. Stoecklinger, C. Lupinek, J. Thalhamer, A. A. Fedorov, S. C. Almo, R. Valenta

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)569-580
Number of pages12
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume64
Issue number4
DOIs
StatePublished - Apr 1 2009

Keywords

  • Allergens
  • Immunotherapy
  • Pollens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ball, T., Linhart, B., Sonneck, K., Blatt, K., Herrmann, H., Valent, P., Stoecklinger, A., Lupinek, C., Thalhamer, J., Fedorov, A. A., Almo, S. C., & Valenta, R. (2009). Reducing allergenicity by altering allergen fold: A mosaic protein of Phl p 1 for allergy vaccination. Allergy: European Journal of Allergy and Clinical Immunology, 64(4), 569-580. https://doi.org/10.1111/j.1398-9995.2008.01910.x