Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy

Autor: Suzanne Quaak, Marianne Witten, Birgit Linhart, E. N. Clare Mills, Bernhard Maderegger, Neil M. Rigby, Ines Swoboda, Jet Heyse, Antonio Portolés, Jaap H. Akkerdaas, Rudolf Valenta, Sonia Vázquez-Cortés, Per Stahl-Skov, Anna Lewandowska-Polak, Lars Blom, Sara Santos-Magadan, Laurian Zuidmeer-Jongejan, Frank Stolz, Carsten Bindslev-Jensen, Heidi J. Schnoor, Rosa Ferrara, Sigurveig T. Sigurdardottir, Juan A. Asturias, Bernard Maillere, Michael Clausen, Maria Livia Bernardi, Georg Stegfellner, George A. Stavroulakis, Montserrat Fernandez-Rivas, Stephan Kopp, Lars K. Poulsen, Ville Ranta-Panula, Ronald van Ree, Claudio Nicoletti, Nikolaos G. Papadopoulos, Adriano Mari, Martina Hauer, Bettina M. Jensen, Angela Neubauer, Hans Huber, Alberto Martínez, Serge A. Versteeg, Marek L. Kowalski
Přispěvatelé: AII - Amsterdam institute for Infection and Immunity, Experimental Immunology, APH - Amsterdam Public Health, [ 1 ] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, NL-1105 AZ Amsterdam, Netherlands [ 2 ] Biomay AG, Vienna, Austria [ 3 ] Med Univ Vienna, Vienna, Austria [ 4 ] Inst Food Res, Norwich NR4 7UA, Norfolk, England [ 5 ] Copenhagen Univ Hosp, Allergy Clin, Gentofte, Denmark [ 6 ] HAL Allergy BV, Leiden, Netherlands [ 7 ] BIAL Aristegui, Bilbao, Spain [ 8 ] Odense Univ Hosp, DK-5000 Odense, Denmark [ 9 ] Ctr Mol Allergol, Ist Dermopat Immacolata, Rome, Italy [ 10 ] Landspitali Univ Hosp Reykjavik, Reykjavik, Iceland [ 11 ] CAAM, Assoc Ctr Mol Allergol, Rome, Italy [ 12 ] Med Univ Lodz, Dept Immunol Rheumatol & Allergy, Lodz, Poland [ 13 ] CEA, Inst Biol Technol, Paris, France [ 14 ] Univ Manchester, Manchester Inst Biotechnol, Manchester Acad Hlth Sci Ctr, Inst Inflammat & Repair, Manchester, Lancs, England [ 15 ] Univ Athens, Pediat Clin 2, Dept Allergy, Athens, Greece [ 16 ] Hosp Clin San Carlos, IdISSC, Dept Clin Pharmacol, Madrid, Spain [ 17 ] Hosp Clin San Carlos, IdISSC, Dept Allergy, Madrid, Spain [ 18 ] Univ Turku, Cent Anim Lab, Turku, Finland [ 19 ] RefLab ApS, Copenhagen, Denmark [ 20 ] Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, NL-1105 AZ Amsterdam, Netherlands
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Protein Folding
medicine.medical_treatment
Gene Expression
Immunoglobulin E
law.invention
Mice
0302 clinical medicine
law
Immunology and Allergy
Good manufacturing practice
ta317
Parvalbumin
biology
Protein Stability
General Medicine
Recombinant Proteins
3. Good health
Parvalbumins
Carp
Recombinant DNA
Female
Immunotherapy
Rabbits
Food Hypersensitivity
Fish Proteins
Carps
Fæðuofnæmi
Injections
Subcutaneous
Immunology
ta3111
Lethal Dose 50
03 medical and health sciences
Allergen mutants
Cyprinus carpio
FAST
Fish
Food allergy
Recombinant hypoallergenic allergens
Toxicity
Allergens
Animals
Calcium-Binding Proteins
Desensitization
Immunologic
Double-Blind Method
Escherichia coli
Humans
Immunoglobulin G
Leukocytes
Mononuclear
medicine
Hypoallergenic
Ofnæmi
biology.organism_classification
medicine.disease
030228 respiratory system
biology.protein
030215 immunology
Zdroj: International archives of allergy and immunology, 166(1), 41-51. S. Karger AG
Zuidmeer-Jongejan, L, Huber, H, Swoboda, I, Rigby, N, Versteeg, S A, Jensen, B M, Quaak, S, Akkerdaas, J H, Blom, L, Asturias, J, Bindslev-Jensen, C, Bernardi, M L, Clausen, M, Ferrara, R, Hauer, M, Heyse, J, Kopp, S, Kowalski, M L, Lewandowska-Polak, A, Linhart, B, Maderegger, B, Maillere, B, Mari, A, Martinez, A, Mills, E N C, Neubauer, A, Nicoletti, C, Papadopoulos, N G, Portoles, A, Ranta-Panula, V, Santos-Magadan, S, Schnoor, H J, Sigurdardottir, S T, Stahl-Skov, P, Stavroulakis, G, Stegfellner, G, Vázquez-Cortés, S, Witten, M, Stolz, F, Poulsen, L K, Fernandez-Rivas, M, Valenta, R & van Ree, R 2015, ' Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy ', International Archives of Allergy and Immunology, vol. 166, no. 1, pp. 41-51 . https://doi.org/10.1159/000371657
ISSN: 1018-2438
DOI: 10.1159/000371657
Popis: Background: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. Objectives: Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1. Methods:Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product. Results: Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability. Conclusion: The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine.
Databáze: OpenAIRE
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