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Reducing allergenicity by altering allergen fold: a mosaic protein of Phl p 1 for allergy vaccination.
Allergy. 2009 Apr; 64(4):569-80.A

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.

Authors+Show Affiliations

Department of Pathophysiology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19243361

Citation

Ball, T, et al. "Reducing Allergenicity By Altering Allergen Fold: a Mosaic Protein of Phl P 1 for Allergy Vaccination." Allergy, vol. 64, no. 4, 2009, pp. 569-80.
Ball T, Linhart B, Sonneck K, et al. Reducing allergenicity by altering allergen fold: a mosaic protein of Phl p 1 for allergy vaccination. Allergy. 2009;64(4):569-80.
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, 64(4), 569-80. https://doi.org/10.1111/j.1398-9995.2008.01910.x
Ball T, et al. Reducing Allergenicity By Altering Allergen Fold: a Mosaic Protein of Phl P 1 for Allergy Vaccination. Allergy. 2009;64(4):569-80. PubMed PMID: 19243361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reducing allergenicity by altering allergen fold: a mosaic protein of Phl p 1 for allergy vaccination. AU - Ball,T, AU - Linhart,B, AU - Sonneck,K, AU - Blatt,K, AU - Herrmann,H, AU - Valent,P, AU - Stoecklinger,A, AU - Lupinek,C, AU - Thalhamer,J, AU - Fedorov,A A, AU - Almo,S C, AU - Valenta,R, Y1 - 2009/02/19/ PY - 2009/2/27/entrez PY - 2009/2/27/pubmed PY - 2009/5/27/medline SP - 569 EP - 80 JF - Allergy JO - Allergy VL - 64 IS - 4 N2 - 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. SN - 1398-9995 UR - https://www.unboundmedicine.com/medline/citation/19243361/Reducing_allergenicity_by_altering_allergen_fold:_a_mosaic_protein_of_Phl_p_1_for_allergy_vaccination_ L2 - https://doi.org/10.1111/j.1398-9995.2008.01910.x DB - PRIME DP - Unbound Medicine ER -