BACKGROUND: A hypoallergen of the major cat allergen Fel d 1, recombinant (r) Fel d 1 (DTE III), was previously shown to have retained T-cell reactivity and strongly reduced IgE-binding capacity compared to unmodified rFel d 1. Here, we evaluated the therapeutic capacity of rFel d 1 (DTE III) in a mouse model for cat allergy. METHODS: Mice were subcutaneously (s.c.) sensitized with rFel d 1 and subsequently treated (s.c.) with 50 or 200 μg rFel d 1 (DTE III), or 50 μg rFel d 1, prior to intranasal challenge with cat dander extract. Airway hyperreactivity (AHR), cells and cytokines in bronchoalveolar lavage fluid, splenocyte in vitro response, and serum immunoglobulins were analyzed. Seven cat-allergic patients and ten healthy controls were tested for skin prick test (SPT) reactivity to rFel d 1 (DTE III) and rFel d 1. RESULTS: Mice treated with 50 and 200 μg rFel d 1 (DTE III), and 50 μg rFel d 1, produced increased serum levels of rFel d 1-specific IgG1 and IgG2a compared to sham-treated mice. IgG from all treatment groups could block binding of patients' IgE to rFel d 1. The 200 μg rFel d 1 (DTE III) treatment tended to reduce AHR. All mice tolerated treatment with rFel d 1 (DTE III), in contrast to only four of ten treated with rFel d 1. Compared to rFel d 1, the hypoallergen showed a tendency of reduced SPT reactivity. CONCLUSION: The rFel d 1 (DTE III) hypoallergen might be a promising candidate for application in immunotherapy of cat allergy with improved safety and efficacy.
BACKGROUND: A hypoallergen of the major cat allergen Fel d 1, recombinant (r) Fel d 1 (DTE III), was previously shown to have retained T-cell reactivity and strongly reduced IgE-binding capacity compared to unmodified rFel d 1. Here, we evaluated the therapeutic capacity of rFel d 1 (DTE III) in a mouse model for cat allergy. METHODS:Mice were subcutaneously (s.c.) sensitized with rFel d 1 and subsequently treated (s.c.) with 50 or 200 μg rFel d 1 (DTE III), or 50 μg rFel d 1, prior to intranasal challenge with cat dander extract. Airway hyperreactivity (AHR), cells and cytokines in bronchoalveolar lavage fluid, splenocyte in vitro response, and serum immunoglobulins were analyzed. Seven cat-allergicpatients and ten healthy controls were tested for skin prick test (SPT) reactivity to rFel d 1 (DTE III) and rFel d 1. RESULTS:Mice treated with 50 and 200 μg rFel d 1 (DTE III), and 50 μg rFel d 1, produced increased serum levels of rFel d 1-specific IgG1 and IgG2a compared to sham-treated mice. IgG from all treatment groups could block binding of patients' IgE to rFel d 1. The 200 μg rFel d 1 (DTE III) treatment tended to reduce AHR. All mice tolerated treatment with rFel d 1 (DTE III), in contrast to only four of ten treated with rFel d 1. Compared to rFel d 1, the hypoallergen showed a tendency of reduced SPT reactivity. CONCLUSION: The rFel d 1 (DTE III) hypoallergen might be a promising candidate for application in immunotherapy of cat allergy with improved safety and efficacy.
Authors: Jurgen Herre; Hans Grönlund; Heather Brooks; Lee Hopkins; Lisa Waggoner; Ben Murton; Monique Gangloff; Olaniyi Opaleye; Edwin R Chilvers; Kate Fitzgerald; Nick Gay; Tom Monie; Clare Bryant Journal: J Immunol Date: 2013-07-22 Impact factor: 5.422
Authors: Christine Y Y Wai; Nicki Y H Leung; Marco H K Ho; Laurel J Gershwin; Shang An Shu; Patrick S C Leung; Ka Hou Chu Journal: PLoS One Date: 2014-11-03 Impact factor: 3.240
Authors: M Curin; M Weber; T Thalhamer; I Swoboda; M Focke-Tejkl; K Blatt; P Valent; K Marth; T Garmatiuk; H Grönlund; J Thalhamer; S Spitzauer; R Valenta Journal: Clin Exp Allergy Date: 2014-06 Impact factor: 5.018