Background: The Dermatophagoides pteronyssinus allergen, Der p 2, is recognized by more than 90% of HDM-allergic patients and induce asthma. Among these patients, 5 to 10 % remain uncontrolled and need innovative approaches based on specific immunotherapy. Genetic engineering led to the development of new therapeutic recombinant hypoallergenic peptides with lower IgE and T-cell reactivity. Objective: To develop a Der p 2 derived peptides and analyze its allergy therapeutic activity in murine and humanized models of experimental allergic asthma Methods: Treatment of allergic asthma was achieved through subcutaneous injection of Der P 2 derived peptide. Treatment efficacy was assessed in a mouse and humanized models of house dust mite induced asthma through percutaneous sensitization. Functional and immune improvement during peptide immunotherapy were evaluated by respiratory function, allergic airway inflammation, lung histology and T helper cells response measurement. Results: Injection of Der p 2 derived peptides inhibits development of airway hyperresponsiveness to methacholine in model of chronic cortico-resistant allergic airway inflammation. Moreover, airway inflammation, IgE production and inflammatory T cells response are also inhibited. Similar effects were also detected in a humanized model of chronic experimental asthma. Interestingly, this peptide exhibits anti-inflammatory properties by inhibiting Th2 and Th17 cell polarization. Conclusion: Our results demonstrate that allergen-specific peptide therapy display similar immunomodulating effect as SCIT or SLIT and should be considered as promising approach for treating respiratory allergies.