Allergen-specific immunotherapy with Der p 1/2 mRNA vaccines alleviates house dust mite-induced allergic airway inflammation in a mouse model

Abstract Allergen-specific immunotherapy is the only treatment that alters the natural course of allergic diseases and provides long-term therapeutic effects. Current treatments are based on crude allergen extracts, which contain various complex components and lack standardization, significantly affecting the safety and efficacy of AIT. With the success of mRNA vaccines, allergen-specific mRNA vaccines could prove to be a viable treatment approach. We screened major house dust mite allergens mRNA sequences in 293T cells and prepared three mRNA vaccines, then tested the safety and efficacy of AIT with these vaccines in a house dust mite-induced allergic airway mouse model. House dust mite-sensitized mice underwent subcutaneous immunotherapy with a house dust mite extract, mRNA vaccines, or placebo. Subsequent to the AIT and challenge, we assessed body temperature, allergen-induced ear swelling, specific immunoglobulin response, inflammatory cells in bronchoalveolar lavage fluid and lung tissues, and cellular immune responses in the spleen, mediastinal lymph nodes, and lungs. Der p 1- and Der p 2 mRNA were successfully expressed in 239T cells and induced specific IgG antibodies in mice. Body temperature monitoring revealed no signs of anaphylaxis following the first subcutaneous injection of either vaccine. Ear swelling response measurements indicated suppression of an early allergic reaction in Der p 2 mRNA-treated mice. All groups demonstrated the ability to suppress airway inflammation and eosinophilic infiltration. Strong differentiation of regulatory T cells and increased effective regulation of the Th1/Th2 balance were observed in mRNA-treated mice. These data suggest that mRNA vaccines represent a potential novel approach for the development of AIT treatments.