Treatment with a Fel d 1 hypoallergen reduces allergic responses in a mouse model for cat allergy.
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.


CONCLUSIONS
The rFel d 1 (DTE III) hypoallergen might be a promising candidate for application in immunotherapy of cat allergy with improved safety and efficacy.
Saarne
T
T
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden. tiiu.saarne@ki.se
Neimert-Andersson
T
T
Grönlund
H
H
Jutel
M
M
Gafvelin
G
G
van Hage
M
M
D000818:Animals; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D016022:Case-Control Studies; D002415:Cats; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D007073:Immunoglobulin E; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D011994:Recombinant Proteins; D016896:Treatment Outcome
D006023:Glycoproteins; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D007073:Immunoglobulin E; C059296:Fel d 1 protein, Felis domesticus