Evaluation of the local tolerance of flagellin aerosol therapy (FLAMOD) on primary human cell-based 3D in vitro nasal, bronchial, small-airway and alveolar models

September 19, 2024

Poster 2024 AIT – Association of Inhalation Toxicology, 17.-19.September 2024, Cleveland, Ohio, USA

Mireille Caul-Futy1, Cindia Ferreira1, Christine Caul-Futy2, Rosy Bonfante1, Itziar Sanjuan2, Edouard Sage3, Mara Baldry2, Song Huang1, Charlotte Green-Jensen4, Nathalie Heuze Vourc’h5, Jean-Claude Sirard2 and Samuel Constant1
1Epithelix, Switzerland
2Institut Pasteur de Lille, France
3Hopital Foch, France
4Statens Serum Institut, Denmark
5Université de Tours, France

Bacterial pneumonia is a major cause of morbidity and mortality in humans. To counter this, the European consortium FAIR aims to develop more efficient therapies, based on recombinant flagellin FliC∆174-400, to treat pneumonia with or without a concomitant uptake of antibiotics. Recombinant flagellin works as an immune-modulator which boosts the innate immunity of airway epithelia via the activation of TLR-5. Delivery of recombinant flagellin to the lung via nebulization has the advantage of directly targeting the airway epithelial cells while conferring minimal systemic immune activation. We herein describe the local tolerance evaluation of a flagellin-based formulation (FLAMOD) for mesh-nebulization on primary human airway and lung epithelial models. Regional effects on fully differentiated nasal, bronchial (MucilAir™), small airways (SmallAir™) and alveolar (AlveolAir™) epithelial function were evaluated using a multi-parametric approach and a dynamic analysis.

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