Reviews and feature articleThe European Union CREATE Project: A model for international standardization of allergy diagnostics and vaccines
Section snippets
Participating organizations and study design
The CREATE consortium comprised 28 organizations: 9 research laboratories, 11 clinical research groups, 6 allergen manufacturers, and 2 biotech companies from 9 European countries (Austria, Denmark, France, Germany, Italy, The Netherlands, Spain, Sweden, and the United Kingdom; see Table E1 in this article's Online Repository at www.jacionline.org). The consortium included 3 laboratories from governmental institutions involved in regulatory affairs: the Paul-Ehrlich Institute (Germany), the
Structural comparisons of purified natural and recombinant allergens
All allergens showed greater than 95% purity when analyzed by means of SDS-PAGE (Fig 2). The molecular weights of allergens produced in E coli showed good agreement with their natural counterparts. Mite allergens produced in P pastoris (rDer p 1 and rDer f 1) had significantly higher molecular weights because they were glycosylated (by using carbohydrates incorporated by P pastoris). Partial amino acid sequencing by means of ESI-QTOF-MS confirmed the identity of the allergens and accounted for
Discussion
The CREATE project had several successful outcomes. The project conducted a thorough structural comparison of purified natural and recombinant allergens and identified several recombinant allergens that are suitable as biologic reference preparations. CREATE provided a strong body of data on the IgE-binding activity of natural and recombinant allergens and has identified ELISA reagents that are suitable for allergen measurement. Three recombinant allergens were considered to be suitable as
A model for international allergen standardization
The CREATE project has provided a major step forward in allergen standardization and provides a coherent strategy for the future development of a comprehensive panel of international allergen standards. The criteria of allergen purity and IgE binding used in CREATE can readily be applied to other allergens. Improvements that have been made in the production of recombinant allergens since the CREATE project was initiated will make it easier to produce high-quality allergens with optimal IgE
References (31)
- et al.
Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper
J Allergy Clin Immunol
(1998) Indoor allergens: relevance of major allergen measurements and standardization
J Allergy Clin Immunol
(2007)- et al.
Recombinant allergens for diagnosis and therapy of allergic disease
J Allergy Clin Immunol
(2000) - et al.
Indoor allergens and asthma: report of the Third International Workshop
J Allergy Clin Immunol
(1997) - et al.
House dust mite allergen in US beds: results from the First National Survey of Lead and Allergens in Housing
J Allergy Clin Immunol
(2003) - et al.
Distribution and determinants of house dust mite allergens in Europe: the European Community Respiratory Health Survey II
J Allergy Clin Immunol
(2006) - et al.
Cat allergen level: its determinants and relationship to specific IgE to cat across European centers
J Allergy Clin Immunol
(2006) - et al.
Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study
Lancet
(2006) - et al.
The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease
J Allergy Clin Immunol
(2000) - et al.
Allergen standardization
J Allergy Clin Immunol
(1991)
Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American academy of Allergy, Asthma and Immunology
Ann Allergy Asthma Immunol
Circular dichroism analysis of allergens
Methods
Immunoglobulin E antibodies that crossreact with vegetable foods, pollen, and Hymenoptera venom
J Allergy Clin Immunol
Analysis of the structure and allergenicity of recombinant pro- and mature Der p 1 and Der f 1: major conformational IgE epitopes blocked by prodomains
J Allergy Clin Immunol
Allergen-specific immunotherapy with recombinant grass pollen allergens
J Allergy Clin Immunol
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Supported in part by the 5th Framework Programme of the European Union (contract no. G6RD-CT-2001-00582) and by the following companies: ALK-Abelló, Allergopharma Joachim Ganzer KG, ASAC Pharmaceutical International SA, Biomay AG, Laboratorios Leti, HAL Allergy BV, Indoor Biotechnologies Ltd, and Stallergènes SA.
Disclosure of potential conflict of interest: M. D. Chapman is co-owner of Indoor Biotechnologies and has received research support from the National Institute for Environmental Health Sciences. F. Ferreira has received research support from Biomay and the Austrian Science Fund and has served as a consultant for Indoor Biotechnologies and the Allergen Online Database. M. Villalba has received research support from Ministerio de Ciencia y Tecnologia and ALK-Abelló. O. Cromwell is employed by Allergopharma Joachim Ganzer. M. Fernández-Rivas has received research support from the European Commission. S. Durham has received research support from GlaxoSmithKline and ALK-Abelló and has served as a member of the Immune Tolerance Network. S. Vieths has received honoraria from Phadia and the Food Allergy Resource and Research Program; is an associate for the Institute for Product Quality; has received research support from the European Union, the German Research Society, the Research Fund of the German Food Industry, Monsanto Company, and the European Directorate for the Quality of Medicines and Health Care; and has served as a member of the European Academy of Allergy and Clinical Immunology, the International Union of Immunological Societies, the European Agency for the Evaluation of Medicinal Products, the European Pharmacopeia Commission, the ILSI Health and Environmental Institute, the Protein Allergenicity Technical Committee, CEN, and Deutsche Gesellschaft fir Allergie und Klinische Immunologie. R. van Ree has consulting arrangements with Stallergènes, BIAL Aristegui, and HAL Allergy BV. The rest of the authors have declared that they have no conflict of interest.