Abstracts selected for oral presentation: EMBRN webinar March 3rd 2021 1 1 Inotodiol ameliorates Th2 mediated airway inflammation by attenuating mast cell activities in a mouse model of asthma

s selected for oral presentation: EMBRN webinar March 3rd 2021 1 1 Inotodiol ameliorates Th2 mediated airway inflammation by attenuating mast cell activities in a mouse model of asthma. Sabin Acharya, Liu Ye, Rema Naskar, Inkyu Hwang. phrsabin@gmail.com Immunology and Immunopharmacology Laboratory, College of Pharmacy, Chungnam National University, 99 Daekak-ro Yuseong-gu, Daejeon 34134, Republic of Korea Inotodiol is a lanostane triterpenoid found only in Chaga mushroom. In a previous study, we have shown that inotodiol holds an activity to suppress the mast cell function in vivo and ease allergy symptoms observed in a chicken ovalbumin (cOVA)-induced mouse model of food allergy. Based on that, we hypothesized that inotodiol could exert a therapeutic effect on Th2mediated allergic asthma where mast cell also plays a critical role and examined the effect with a mouse model of allergic asthma. For inducing asthmatic symptoms, Balb/c mice were sensitized with cOVA on days 1 and 14 (i.p.), followed by challenges with aerosolized cOVA on days 23, 24, 25, 26, 27, 30, and 31. Groups of mice were treated with inotodiol by oral gavage for the last five days of challenges at either 2 or 6 mg per kg body weight (mpk). Twenty-four hours after the last challenge, respiratory mechanics were evaluated with the forced oscillation technique (flexivent). Inotodiol-treated mice (6 mpk) showed a significant improvement in the overall respiratory resistance and the total elastance in response to methacholine challenges. The inflammatory lesions and the goblet cell hyperplasia in the airway mucosa were also found to be reduced by the inotodiol treatments. Supporting the idea that the anti-asthmatic effect of inotodiol is attributed to the inhibition of mast cell function, the levels of mast cell-specific protease-1 (MCPT-1) in bronchoalveolar lavage (BAL) fluid of inotodiol-treated mice not only were lowered by the treatments in a dose-dependent manner but also showed a strong correlation with the severities of the asthmatic symptoms. Additionally, the numbers of mast cells populating in the airway mucosa were also markedly decreased following the inotodiol-treatments. Together, it is indicated that inotodiol can be developed as a new effective and safe oral medication for the treatment of Th2-mediated eosinophilic asthma whose symptoms are often instigated by the activation of mast cells. Abstracts selected for oral presentation: EMBRN webinar March 3rd 2021s selected for oral presentation: EMBRN webinar March 3rd 2021 2 2 Anti-IgE vaccination prevents human IgE-mediated severe anaphylaxis in humanized mice Eva Conde 2, , Marija Backovic , Julien Stackowicz , Ophélie Godon, Samir Hamdi, Bernard Malissen, Frédéric Fiore, Vincent Serra, Pierre Bruhns , Laurent L. Reber 5, . laurent.reber@inserm.fr; eva.conde-garcia@inserm.fr 1 Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM, F-75015 Paris, France. 2 Sorbonne Université, ED394, F-75005 Paris, France 3 Neovacs SA, F-75014 Paris, France. 4 Unit of Structural Virology, Institut Pasteur, UMR 3569 CNRS, F-75015 Paris, France. 5 Toulouse Institute for Infectious and Inflammatory Diseases, Infinity. UMR 1291 INSERM, Toulouse, France. 6 Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, F-13288 Marseille, France. equal contribution. Anaphylaxis is the most dramatic clinical manifestation of allergy. In allergic subjects, the allergen is recognized by allergen-specific IgE bound to the receptor FcεRI on mast cells, which promotes degranulation of these cells and the release of mediators, including histamine. We developed a vaccine strategy against IgE to induce long-term protection from IgE-mediated mast cell activation. A fragment of human IgE was used to generate a conjugate vaccine technology termed kinoid. To assess the efficacy of IgE vaccination, we generated a mouse model humanized for IgE and its high-affinity receptor FcεRI. IgE vaccination induced longterm production of anti-human IgE neutralizing antibodies without any detectable adverse effect. It reduced both circulating and FcεRI-bound human IgE, and protected against severe IgE-mediated anaphylaxis in IgE/FcεRI humanized mice. Thus, IgE vaccination represents a promising, cost-effective, long-term therapeutic strategy for the treatment of IgE-mediated anaphylaxis, and other IgEand mast cell-driven allergic conditions. Abstracts selected for oral presentation: EMBRN webinar March 3rd 2021s selected for oral presentation: EMBRN webinar March 3rd 2021