A Cutaneous immunotherapy for peanut allergy

Summary: Abstract Body: Treatment of peanut allergy (PA) remains recalcitrant to improvement owing to the fundamental safety and efficacy limitations of existing therapeutic approaches. Here, we report on the progress of our novel microneedle patch (MNP)-based immunotherapy strategy to treat PA. Our approach leverages the power of the skin immune system via co-delivery of peanut extract (PE) and rationally selected immune modifiers with MNPs to induce PE-specific neutralizing IgG and Treg responses in a well-tolerated fashion to reverse the symptoms of PA. First, we established a new murine model of PA through cutaneous sensitization via co-delivery of PE and a Th2-skewing adjuvant. This model recapitulated the key features of atopic skin, such as impaired barrier function and heightened local inflammation with Th2-predominant pro-inflammatory cytokines. This model also exhibited the systemic hallmarks of clinical PA, such as Th2 responses and elevated peanut-specific serum IgE levels. Mimicking these key local and global features of skin-sensitized PA patients in an experimental model facilitated the robust induction of anaphylaxis in upon systemic challenge with PE, indicated by increased clinical symptoms. Anaphylaxis was further confirmed by evident hypothermia and higher serum levels of systemic anaphylaxis mediators, such as mast cell protease-1 (MCPT-1) in sensitized mice with respect to control (unsensitized) mice upon a systemic challenge with PE. Next, we used this model to test the efficacy of our MNP-based PA immunotherapy. Murine studies showed that MNP-directed PA immunotherapy elicited increased PE-specific IgG and Treg responses, as well as improved Th1-skewing compared with MNPs loaded with PE alone. Notably, MNP-based PA immunotherapy prevented anaphylaxis, determined by significantly reduced hypothermia, clinical scores, and systemic levels of MCPT-1 in treated mice compared with control (sensitized and untreated) mice upon systemic challenge with PE. These findings support the further development of MNP-based cutaneous immunotherapies for PA. Ashish Dhayani¹, Stephen Balmert¹, Cara D. Carey¹, Emrullah Korkmaz¹, Louis D. Falo, Jr.¹ 1. Dermatology, University of Pittsburgh, Pittsburgh, PA, United States. Adaptive and Auto-Immunity