Authors: Nada S. Alakhras, Jaeho Shin, Scott A. Smith, Anthony L. Sinn, Wenwu Zhang, Gyoyeon Hwang, Jenna Sjoerdsma, Emily K. Bromley, Karen E. Pollok, Basar Bilgicer, Mark H. Kaplan
Published: 2023-02-08
DOI: 10.1126/scitranslmed.add6373
Source: Full article
Peanut-induced allergy is an immunoglobulin E (IgE)–mediated type I hypersensitivity reaction that manifests symptoms ranging from local edema to life-threatening anaphylaxis. Although there are treatments for symptoms in patients with allergies resulting from allergen exposure, there are few preventive therapies other than strict dietary avoidance or oral immunotherapy, neither of which are successful in all patients. We have previously designed a covalent heterobivalent inhibitor (cHBI) that binds in an allergen-specific manner as a preventive for allergic reactions. Building on previous in vitro testing, here, we developed a humanized mouse model to test cHBI efficacy in vivo. Nonobese diabetic–severe combined immunodeficient γc-deficient mice expressing transgenes for human stem cell factor, granulocyte-macrophage colony-stimulating factor, and interleukin-3 developed mature functional human mast cells in multiple tissues and displayed robust anaphylactic reactions when passively sensitized with patient-derived IgE monoclonal antibodies specific for peanut