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1. Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice.

Author

Conde E, Bertrand R, Balbino B, Bonnefoy J, Stackowicz J, Caillot N, Colaone F, Hamdi S, Houmadi R, Loste A, Kamphuis JBJ, Huetz F, Guilleminault L, Gaudenzio N, Mougel A, Hardy D, Snouwaert JN, Koller BH, Serra V, Bruhns P, Grouard-Vogel G, and Reber LL

Subjects
Animals, Asthma immunology, Bacterial Proteins administration & dosage, Bacterial Proteins immunology, Chronic Disease therapy, Disease Models, Animal, Female, Humans, Injections, Intramuscular, Interleukin-13 genetics, Interleukin-13 immunology, Interleukin-4 genetics, Interleukin-4 immunology, Mice, Mice, Transgenic, Vaccines, Conjugate administration & dosage, Vaccines, Conjugate immunology, Asthma therapy, Interleukin-13 antagonists & inhibitors, Interleukin-4 antagonists & inhibitors, Vaccination methods
Abstract

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.

Published
2021
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2. Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice

Author

Conde, Eva, Bertrand, Romain, Balbino, Bianca, Bonnefoy, Jonathan, Stackowicz, Julien, Caillot, Noémie, Colaone, Fabien, Hamdi, Samir, Houmadi, Raïssa, Loste, Alexia, Kamphuis, Jasper, Huetz, François, Guilleminault, Laurent, Gaudenzio, Nicolas, Mougel, Aurélie, Hardy, David, Snouwaert, John, Koller, Beverly, Serra, Vincent, Bruhns, Pierre, Grouard-Vogel, Géraldine, Reber, Laurent, 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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), Gestionnaire, Hal Sorbonne Université, APPEL À PROJETS GÉNÉRIQUE 2018 - Développement d'un vaccin thérapeutique pour les maladies allergiques - - AllergyVACS2018 - ANR-18-CE18-0023 - AAPG2018 - VALID, ERC-2018-STG - 802041 - INCOMING, Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples - MYELOSHOCK - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616050 - VALID, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut Pasteur [Paris]-Université de Paris (UP), and 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)

Subjects
MESH: Mice, Transgenic, Science, MESH: Asthma / immunology, [SDV]Life Sciences [q-bio], MESH: Asthma / therapy, MESH: Vaccines, Conjugate / immunology, Mice, Transgenic, Injections, Intramuscular, MESH: Chronic Disease / therapy, Mice, Bacterial Proteins, Animals, Humans, MESH: Interleukin-13 / genetics, MESH: Animals, MESH: Interleukin-4 / antagonists & inhibitors, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Interleukin-13, Vaccines, Conjugate, MESH: Vaccines, Conjugate / administration & dosage, MESH: Humans, MESH: Interleukin-4 / genetics, Interleukins, Vaccination, MESH: Vaccination / methods, Chronic inflammation, MESH: Injections, Intramuscular, Asthma, MESH: Interleukin-13 / immunology, respiratory tract diseases, Conjugate vaccines, MESH: Interleukin-13 / antagonists & inhibitors, [SDV] Life Sciences [q-bio], Disease Models, Animal, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Bacterial Proteins / administration & dosage, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Chronic Disease, MESH: Interleukin-4 / immunology, MESH: Bacterial Proteins / immunology, Female, Interleukin-4, MESH: Disease Models, Animal, MESH: Female, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract

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.

Published
2021

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