Immunization with an adeno-associated viral vectored allergy vaccine containing Der p1-Der p2 effectively alleviates an asthmatic phenotype in mice

Given the rising incidence of allergic asthma, current symptomatic treatments primarily offer relief rather than halt disease progression. Recombinant allergens, designed with reduced immunoglobulin E (IgE) reactivity and the ability to regulate excessive T helper type 2 (Th2) responses, are emerging as promising candidates for more precise, effective, and safer specific immunotherapy (SIT). SIT remains the only clinical approach capable of potentially curing certain allergic diseases by inducing immunological tolerance. In this study, we explored the protective effects of AAV-Dp12S, an adeno-associated viral vector carrying two house dust mite antigens, Der p1 and Der p2, against allergic asthma. Using a murine model of HDM, immunization with this combination vaccine significantly attenuated the HDM-induced asthmatic phenotype. Invasive lung function assessments revealed improvements following AAV-Dp12S treatment, correlating with marked reductions in goblet cell hyperplasia and pulmonary eosinophilia. Moreover, total serum IgE, HDM-specific IgE (sIgE) titers, and pulmonary inducible nitric oxide synthase levels were effectively reduced. The cytokine profiles in bronchoalveolar lavage fluid (BALF) were modulated, as indicated by decreased levels of type 2 cytokines—interleukin (IL)-4, IL-5, and IL-13—and increased levels of interferon-γ (IFN-γ) and IL-10. Additionally, sIgE titers and production were significantly lowered. Overall, these findings demonstrate the potential of AAV-Dp12S as a therapeutic strategy for both tolerance induction and vaccination in the treatment of allergic asthma.