Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Versteeg, Serge A
Jensen, Bettina M
Akkerdaas, Jaap H
Bernardi, Maria L
Kowalski, Marek L
Mills, E N Clare
Papadopoulos, Nikolaos G
Schnoor, Heidi J
Sigurdardottir, Sigurveig T
Poulsen, Lars K
van Ree, Ronald
MetadataShow full item record
CitationInt. Arch. Allergy Immunol. 2015, 166 (1):41-51
AbstractThe 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.
Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1.
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.
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.
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.
DescriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.
RightsArchived with thanks to International archives of allergy and immunology
- Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy.
- Authors: Freidl R, Gstoettner A, Baranyi U, Swoboda I, Stolz F, Focke-Tejkl M, Wekerle T, van Ree R, Valenta R, Linhart B
- Issue date: 2017 Jun
- In vivo allergenic activity of a hypoallergenic mutant of the major fish allergen Cyp c 1 evaluated by means of skin testing.
- Authors: Douladiris N, Linhart B, Swoboda I, Gstöttner A, Vassilopoulou E, Stolz F, Valenta R, Papadopoulos NG
- Issue date: 2015 Aug
- Recombinant carp parvalbumin, the major cross-reactive fish allergen: a tool for diagnosis and therapy of fish allergy.
- Authors: Swoboda I, Bugajska-Schretter A, Verdino P, Keller W, Sperr WR, Valent P, Valenta R, Spitzauer S
- Issue date: 2002 May 1
- A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy.
- Authors: Swoboda I, Bugajska-Schretter A, Linhart B, Verdino P, Keller W, Schulmeister U, Sperr WR, Valent P, Peltre G, Quirce S, Douladiris N, Papadopoulos NG, Valenta R, Spitzauer S
- Issue date: 2007 May 15
- A general strategy for the generation of hypoallergenic molecules for the immunotherapy of fish allergy.
- Authors: Swoboda I, Balic N, Klug C, Focke M, Weber M, Spitzauer S, Neubauer A, Quirce S, Douladiris N, Papadopoulos NG, Valenta R
- Issue date: 2013 Oct