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

Eva Conde, Romain Bertrand, Bianca Balbino, Jonathan Bonnefoy, Julien Stackowicz, Noémie Caillot, Fabien Colaone, Samir Hamdi, Raïssa Houmadi, Alexia Loste, Jasper B. J. Kamphuis, François Huetz, Laurent Guilleminault, Nicolas Gaudenzio, Aurélie Mougel, David Hardy, John N. Snouwaert, Beverly H. Koller, Vincent Serra, Pierre Bruhns, Géraldine Grouard-Vogel and Laurent L. Reber ()
Additional contact information
Eva Conde: Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM
Romain Bertrand: Neovacs SA
Bianca Balbino: Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM
Jonathan Bonnefoy: Neovacs SA
Julien Stackowicz: Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM
Noémie Caillot: Neovacs SA
Fabien Colaone: Neovacs SA
Samir Hamdi: Neovacs SA
Raïssa Houmadi: University Toulouse III
Alexia Loste: University Toulouse III
Jasper B. J. Kamphuis: University Toulouse III
François Huetz: Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM
Laurent Guilleminault: University Toulouse III
Nicolas Gaudenzio: University Toulouse III
Aurélie Mougel: University Toulouse III
David Hardy: Institut Pasteur, Experimental Neuropathology Unit
John N. Snouwaert: University of North Carolina at Chapel Hill
Beverly H. Koller: University of North Carolina at Chapel Hill
Vincent Serra: Neovacs SA
Pierre Bruhns: Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM
Géraldine Grouard-Vogel: Neovacs SA
Laurent L. Reber: Unit of Antibodies in Therapy and Pathology, Institut Pasteur, UMR 1222 INSERM

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22834-5

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