Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy - 11/05/15
Abstract |
Background |
Grass pollen is one of the most important sources of respiratory allergies worldwide.
Objective |
This study describes the development of a grass pollen allergy vaccine based on recombinant hypoallergenic derivatives of the major timothy grass pollen allergens Phl p 1, Phl p 2, Phl p 5, and Phl p 6 by using a peptide-carrier approach.
Methods |
Fusion proteins consisting of nonallergenic peptides from the 4 major timothy grass pollen allergens and the PreS protein from hepatitis B virus as a carrier were expressed in Escherichia coli and purified by means of chromatography. Recombinant PreS fusion proteins were tested for allergenic activity and T-cell activation by means of IgE serology, basophil activation testing, T-cell proliferation assays, and xMAP Luminex technology in patients with grass pollen allergy. Rabbits were immunized with PreS fusion proteins to characterize their immunogenicity.
Results |
Ten hypoallergenic PreS fusion proteins were constructed, expressed, and purified. According to immunogenicity and induction of allergen-specific blocking IgG antibodies, 4 hypoallergenic fusion proteins (BM321, BM322, BM325, and BM326) representing Phl p 1, Phl p 2, Phl p 5, and Phl p 6 were included as components in the vaccine termed BM32. BM321, BM322, BM325, and BM326 showed almost completely abolished allergenic activity and induced significantly reduced T-cell proliferation and release of proinflammatory cytokines in patients' PBMCs compared with grass pollen allergens. On immunization, they induced allergen-specific IgG antibodies, which inhibited patients' IgE binding to all 4 major allergens of grass pollen, as well as allergen-induced basophil activation.
Conclusion |
A recombinant hypoallergenic grass pollen allergy vaccine (BM32) consisting of 4 recombinant PreS-fused grass pollen allergen peptides was developed for safe immunotherapy of grass pollen allergy.
Le texte complet de cet article est disponible en PDF.Key words : Grass pollen allergy, allergen, recombinant allergen, recombinant hypoallergenic allergen derivative, allergen-specific immunotherapy, peptide-carrier technology
Abbreviations used : CFA, KLH, SIT
Plan
| Supported by research grants from the Christian Doppler Research Association, Vienna, Austria; Biomay AG, Vienna, Austria; and the Austrian Science Fund (FWF), projects F4604, F4605, F4611, and F4613. |
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| Disclosure of potential conflict of interest: This study was funded by the Austrian Science Fund (FWF), the Christian Doppler Research Association, and a research grant from Biomay AG. H. Huber is a board member of Biomay AG, where he is employed. R. Henning is a board member of Biomay AG, from which his institution has received consultancy fees and from which he has received stock or stock options. B. Maderegger is employed by Biomay AG, as is A. Neubauer, G. Stegfellner, M. Hauer, and F. Stolz. V. Niederberger has received consultancy fees from Biomay AG, has received grants or has grants pending from the Austrian Science Fund and the Medical University of Vienna, and has received payment for delivering lectures from Thermo Fisher and Meda Pharmaceuticals. K. Marth has received payments for delivering lectures from Thermo Fisher. R. Weiss's institution has received funding from Biomay AG. P. Valent has received consultancy fees from Novartis, has received or has grants pending from Novartis, and has received payment for delivering lectures from Bristol-Myers Squibb, Novartis, and Pfizer. R. Valenta has received consultancy fees from Biomay AG and has received or has grants pending from Thermo Fisher and Biomay AG. The rest of the authors declare that they have no other relevant conflicts of interest. |
Vol 135 - N° 5
P. 1207 - mai 2015 Retour au numéro
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