PT  - JOURNAL ARTICLE
AU  - Caroline Chupin
AU  - Andrés Pizzorno
AU  - Aurélien Traversier
AU  - Pauline Brun
AU  - Daniela Ogonczyk-Makowska
AU  - Blandine Padey
AU  - Cédrine Milesi
AU  - Victoria Dulière
AU  - Emilie Laurent
AU  - Thomas Julien
AU  - Marie Galloux
AU  - Bruno Lina
AU  - Jean-François Eléouët
AU  - Karen Moreau
AU  - Marie-Eve Hamelin
AU  - Olivier Terrier
AU  - Guy Boivin
AU  - Julia Dubois
AU  - Manuel Rosa-Calatrava
TI  - A novel effective live-attenuated human metapneumovirus vaccine candidate produced in the serum-free suspension DuckCelt®-T17 cell platform
AID  - 10.1101/2021.08.30.458186
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.30.458186
4099  - http://biorxiv.org/content/early/2021/08/30/2021.08.30.458186.short
4100  - http://biorxiv.org/content/early/2021/08/30/2021.08.30.458186.full
AB  - Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen for which there is currently no specific treatment or licensed vaccine. Different strategies have been evaluated to prevent this infection, including the use of live-attenuated vaccines (LAVs). However, further development of LAV approaches is often hampered by the lack of highly efficient and scalable cell-based production systems that support worldwide vaccine production. In this context, avian cell lines cultivated in suspension are currently competing with traditional cell platforms used for viral vaccine manufacturing. We investigated whether the DuckCelt®-T17 avian cell line (Vaxxel) we previously described as an efficient production system for several influenza strains could also be used to produce a new HMPV LAV candidate (Metavac®), an engineered SH gene-deleted mutant of the A1/C-85473 strain of HMPV. To that end, we characterized the operational parameters of multiplicity of infection (MOI), cell density, and trypsin addition to achieve optimal production of the LAV Metavac® in the DuckCelt®-T17 cell line platform. We demonstrated that the DuckCelt®-T17 cell line is permissive and is 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, as well as its capacity to induce efficient neutralizing antibodies in a mouse model. Our results suggest that the DuckCelt®-T17 avian cell line is a very promising platform for scalable in-suspension serum-free production of the HMPV-based LAV candidate Metavac®.Competing Interest StatementThe authors declare the following patent applications : patent FR1856801, pending patent concerning the characterization of the new HMPV-derived LAV METAVAC, applicants : Universite Laval, Centre National de la Recherche Scientifique CNRS, Universite Claude Bernard Lyon 1 UCBL, Institut National de la Sante et de la Recherche Medicale INSERM, Ecole Normale Superieure de Lyon, inventors : Manuel Rosa-Calatrava, Guy Boivin, Julia Dubois, Mario Andres Pizzorno, Olivier Terrier, Marie-Eve Hamelin; patent FR1872957, pending patent concerning the use of the DuckCelt-T17 cell line for METAVAC production, applicants : Universite Laval, Centre National de la Recherche Scientifique CNRS, Universite Claude Bernard Lyon 1 UCBL, Institut National de la Sante et de la Recherche Medicale INSERM, Ecole Normale Superieure de Lyon, inventors : Manuel Rosa-Calatrava, Guy Boivin, Julia Dubois, Mario Andres Pizzorno, Olivier Terrier, Aurelien Traversier. Manuel Rosa-Calatrava, Guy Boivin, Julia Dubois and Marie-Eve Hamelin are co-founders of Vaxxel SAS. Julia Dubois and Caroline Chupin are currently employees of Vaxxel SAS. The funders of the study had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.