Recombinant multimeric dog allergen prevents airway hyperresponsiveness in a model of asthma marked by vigorous TH 2 and TH 17 cell responses.

BACKGROUND: Allergy to dogs affects around 10% of the population in developed countries. Immune therapy of allergic patients with dog allergen extracts has shown limited therapeutic benefit. METHODS: We established a mouse model of dog allergy by repeatedly administering dog dander and epithelium extracts via the intranasal route. We also assessed the efficacy of a recombinant multimeric protein containing Can f 1, f 2, f 4 and f 6 in preventing inflammatory responses to dog extracts. RESULTS: Repeated inhalation of dog extracts induced infiltration of the airways by TH 2 cells, eosinophils and goblet cells, reminiscent of the house dust mite (HDM) model of asthma. Dog extracts also induced robust airway hyperresponsiveness and promoted TH 17 cell responses, which was associated with a high neutrophilic infiltration of the airways. scRNA-Seq analysis of T helper cells in the airways pinpointed a unique gene signature for TH 17 cells. Analysis of T-cell receptors depicted a high frequency of clones that were shared between TH 17, TH 2 and suppressive Treg cells, indicative of a common differentiation trajectory for these subsets. Importantly, sublingual administration of multimeric Can f 1-2-4-6 protein prior to sensitization reduced airway hyperresponsiveness and type 2-mediated inflammation in this model. CONCLUSION: Dog allergen extracts induce robust TH 2 and TH 17 cell-mediated responses in mice. Recombinant Can f 1-2-4-6 can induce tolerance to complex dog allergen extracts.

Allergens in dog extracts: Implication for diagnosis and treatment.

BACKGROUND: Five to ten percent of the population in affluent countries are allergic to dog. Diagnosis and treatment is based on allergen extracts from natural sources where composition and concentration are poorly defined. OBJECTIVE: We aimed to quantify six dog allergens (Can f 1-6) in commercial skin prick test (SPT) solutions and to determine individual allergen profiles in dogs. METHOD: The allergen content of SPT solutions from five vendors and allergen source material from three anatomical sites were analyzed. Fur and saliva samples were collected from a mixed population of 120 dogs. Can f 1-6 were quantified by inhibition ELISA using purified recombinant or natural allergens and polyclonal or monoclonal antibodies. Allergenicity was analyzed by basophil activation test. RESULTS: Extensive variation in allergen composition was observed in commercial SPT vials resulting in a patient-dependent ability to activate basophils. Extract heterogeneity depended on collection site and allergen composition in individual dogs and source materials. Can f 2 and Can f 6 exhibited low levels in fur and SPT solutions, whereas Can f 4, which was the dominating allergen in fur samples, did not display similar high proportions in SPT solutions. Can f 3 varied most among SPT solutions. CONCLUSION: There is a great variation of dog allergens in natural extracts raising questions of source, sampling, processing and ultimately of standardization and minimum allergen levels for accurate diagnosis and treatment.