B, Outline of the treatment groups. lung tissue and BAL fluid. Moreover, DerP1/2SCIT treatment is uniquely able suppress CCL20 and showed a trend toward suppression of IL33, CCL17 and eotaxin levels in lung tissue. hSNF2b == Discussion == Taken together, these data show that purified DerP1/2SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDMinduced activation of Beclometasone lung structural cells including airway epithelium. == Conclusions == We postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT. Keywords:Allergenspecific immunotherapy, allergic asthma, house dust mites, purified natural Der p1 and 2, tolerance induction == 1. INTRODUCTION == Allergenspecific immunotherapy (SIT) has been used for the treatment of allergic disorders for over a century.1Specific immunotherapy (SIT) has been shown to induce durable immunological changes in response to the allergen, through generating neutralizing antibodies, through suppressing numbers and activity of allergenspecific Th2 cells and type 2 innate lymphoid cells (ILC2s), and by inducing regulatory Tcell activity.2Successful SIT has been associated with enhanced release of IL10 in PBMC cultures restimulated with allergen,3serumdependent suppression of crosspresentation by B cells,4and selective loss of those Tcell clones with allergenepitope specificities that are increased in atopic individuals compared to healthy controls.5,6Specific immunotherapy (SIT) induces longterm tolerance to the allergen, as evidenced by the absence of allergic manifestations upon repeated allergen challenges. 1 Current SIT regimens routinely Beclometasone employ a crude extract of the allergen for injection, subcutaneous immunotherapy (SCIT) or tablet and droplet formulation, sublingual immunotherapy (SLIT). Crude Beclometasone extracts contain the full array of major allergens that a patient can be sensitized to, which increases likelihood of therapeutic efficacy in patients without the need of componentresolved diagnosis prior to treatment. Additionally, crude extracts also contain numerous nonprotein constituents such as chitins, glucans, and endotoxins, all of which can act on innate immune cells in a proinflammatory fashion, which might interfere with the toleranceinducing capacity required for successful therapy.7In contrast, use of purified proteins allows for treatment with specific allergens in the absence of such components contained within extracts.8This is expected to enhance SIT efficacy by more efficiently inducing a tolerogenic response due to the absence of TLR agonists during allergen administration, harnessing an immunoregulatory phenotype of the allergenpresenting cell upon SCIT.1Moreover, use of purified allergens in combination with a componentresolved diagnosis of sensibilization patterns holds the promise of personalized intervention strategies in immunotherapy.8However, it is currently unknown whether purified allergens are a more efficient treatment modality than full allergen extracts. House dust mite (HDM) is the most prominent source of indoor exposure to allergens and is a cause for allergic rhinitis and asthma.9The HDM speciesDermatophagoides pteronyssinus(Der p) has at least 23 major allergens9that are thought to contribute to allergic sensitization through their proteolytic activity, activating cells of the innate immune system and priming an adaptive type 2 immune response.2,9In the MAS prospective birth cohort, sensitization patterns for HDM allergens were studied into detail by componentresolved analysis.10Herein, specific IgE (spIgE) for Der p1, 2, and 23 can be detected before sensitization to any of the other major allergens. Moreover, sensitization to Der p1, 2, and 23 allergens has the highest prevalence, with more than half of the 20yearold individuals having spIgE to group 1 and 2 allergens.10Interestingly, early onset of sensitization to group 1, 2, or 23 allergens was associated with sensitization to more HDM allergens and with allergic rhinitis and asthma at school age, indicating the clinical relevance of these sensitization patterns.10Treatment options for HDM allergy include allergen avoidance and SIT.11However, HDM extracts are variable in content of allergens,12,13and stability is Beclometasone limited.14Given the fact that sensitization to Der p1 and 2 identifies more than 95% of HDMallergic individuals9,13and their causal role in early sensitization,10SIT with purified Der p1 and 2 might be a more attractive therapeutic approach compared to the use of HDM extracts. Here, we test the hypothesis that treatment with natural purified Der p1 and 2 is an effective treatment in inducing a protective neutralizing antibody response and in suppressing allergic inflammation in a mouse model of HDMdriven allergic asthma. We find that SCIT with a mixture of Der p1 and 2 is superior to extract in suppressing Th2 cell activity and inducing neutralizing antibodies, and equally capable of suppressing manifestations of allergic airway inflammation upon.