The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with traditional cell platforms used for viral vaccine manufacture. We investigated whether the DuckCelt^®-T17 avian cell line (Vaxxel), previously described as an efficient production system for several influenza strains, could also be used to produce a new HMPV LAV candidate (Metavac^®, SH gene-deleted A1/C-85473 HMPV). To that end, we characterized the operational parameters of MOI, cell density, and trypsin addition to achieve the optimal production of Metavac^®, and demonstrated that the DuckCelt^®-T17 cell line is permissive and well-adapted to the production of the wild-type A1/C-85473 HMPV and the Metavac^® vaccine candidate. Moreover, our results confirmed that the LAV candidate produced in DuckCelt^®-T17 cells conserves its advantageous replication properties in LLC-MK2 and 3D-reconstituted human airway epithelium models, and its capacity to induce efficient neutralizing antibodies in a BALB/c mouse model. Our results suggest that the DuckCelt^®-T17 avian cell line is a very promising platform for the scalable in-suspension serum-free production of the HMPV-based LAV candidate Metavac^®.

Lower respiratory infections, mostly caused by viral or bacterial pathogens, remain a leading global cause of mortality. The differences between animal models and humans contribute to inefficiencies in drug development, highlighting the need for more relevant and predictive, non-animal models. In this context, AlveolAir™, a fully primary in vitro 3D human alveolar model, was characterized and demonstrated the sustained presence of alveolar type I (ATI) and type II (ATII) cells. This model exhibited a functional barrier over a 30-day period, evidenced by high transepithelial electrical resistance (TEER). These findings were further validated by tight junctions’ confocal microscopy and low permeability to Lucifer yellow, confirming AlveolAir™ as robust platform for drug transport assays. Additionally, successful infections with H1N1 and SARS-CoV-2 viruses were achieved, and antiviral treatments with Baloxavir and Remdesivir, respectively, effectively reduced viral replication. Interestingly, both viruses infected only the epithelial layer without replicating in endothelial cells. These findings indicate AlveolAir™ as a relevant model for assessing the toxicity and permeability of xenobiotics and evaluating the efficacy of novel antiviral therapies.