Contributors: Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM); Physiologie, physiopathologie et thérapeutique (ED 394); Sorbonne Université (SU); Neovacs S.A Paris; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity); Université Toulouse III - Paul Sabatier (UT3); Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Neuropathologie expérimentale / Experimental neuropathology; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); University of North Carolina Chapel Hill (UNC); University of North Carolina System (UNC); E.C. is the recipient of a CIFRE Ph.D. fellowship. B.B. was supported partly by a stipend from the Pasteur—Paris University (PPU) International Ph.D. program, and a fellowship from the French “Fondation pour la Recherche Médicale FRM”. N.G. acknowledges funding from the European Research Council (ERC-2018-STG, No. 802041) and the INSERM ATIP-Avenir program, B.H.K. acknowledges funding from the National Institutes of Health (NIH) HL093735 and an Award from the American Asthma Foundation. L.L.R. acknowledges support from the ATIP-Avenir program, and P.B. from the European Research Council (ERC)–Seventh Framework Program (ERC-2013-CoG 616050). This work was supported by a grant from the French National Research Agency ANR-18-CE18-0023 “AllergyVACS”, NEOVACS, the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Institut Pasteur.; ANR-18-CE18-0023,AllergyVACS,Développement d'un vaccin thérapeutique pour les maladies allergiques(2018); European Project: 802041; European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014)
نبذة مختصرة : International audience ; Allergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.
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