title: Covalent coupling of vitamin D3 to the major cat allergen Fel d 1 improves the effects of allergen-specific immunotherapy in a mouse model for cat allergy.
abstract: BACKGROUND
  Allergen-specific immunotherapy (SIT) is currently the only curative treatment for allergy but the treatment needs to be improved. We hypothesize that covalent coupling of immunomodulating vitamin D3 to the major cat allergen Fel d 1 can enhance the beneficial effects of SIT to cat allergy.
  
  
  METHODS
  We treated mice sensitized to Fel d 1 with subcutaneous injections of two doses of recombinant Fel d 1 coupled to 1α,25-dihydroxyvitamin D3 (rFel d 1:VD3) and compared to treatment with the same doses of rFel d 1 in a mouse model for cat allergy. Airway hyperresponsiveness (AHR), cytokines and cells in bronchoalveolar lavage (BAL), in vitro activation of splenocytes to rFel d 1, and Fel d 1-specific immunoglobulins were evaluated.
  
  
  RESULTS
  Treatment with both doses of rFel d 1:VD3 decreased AHR, cellular influx and Th2 cytokines in BAL compared to untreated mice. High- and low-dose rFel d 1 treatment also decreased AHR and BAL Th2 cytokines, with less decrease for the low-dose treatment. Importantly, the total number of cells and eosinophils in BAL was markedly reduced at both high- and low-dose rFel d 1:VD3 compared to treatment with rFel d 1 alone. Finally, treatment with both rFel d 1 and rFel d 1:VD3 induced Fel d 1-specific serum IgG.
  
  
  CONCLUSIONS
  Our results indicate a beneficial therapeutic effect of rFel d 1:VD3 on airway inflammation, AHR and rFel d 1-specific immune responses and thus suggest that this novel immunomodulatory candidate may improve both the efficacy and safety of SIT.
authors: Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden.
authors: Jeanette
authors: J
authors: Grundström
authors: Theresa
authors: T
authors: Neimert-Andersson
authors: Cecilia
authors: C
authors: Kemi
authors: Ola B
authors: OB
authors: Nilsson
authors: Tiiu
authors: T
authors: Saarne
authors: Mats
authors: M
authors: Andersson
authors: Marianne
authors: M
authors: van Hage
authors: Guro
authors: G
authors: Gafvelin
mesh_terms: D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D019138:Antibodies, Blocking / Q000097:blood / Q000276:immunology; D018893:Bronchoalveolar Lavage; D002415:Cats / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002762:Cholecalciferol / Q000737:chemistry / Q000627:therapeutic use*; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D004804:Eosinophils; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology
chemical_list: D000485:Allergens; D019138:Antibodies, Blocking; D006023:Glycoproteins; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D015848:Interleukin-5; D002762:Cholecalciferol; C059296:Fel d 1 protein, Felis domesticus