METAVAC-T17: Characterization and up-scaling of a DuckCeltTM-T17 cell suspension culture process for the production of a new live-attenuated HRSV/HMPV chimeric METApneumovirus-based VACcine

Durée :36 mois

Participants :VIRPATH

• Porteur pour le partenaire UCBL : Claire Bordes
• Instrument : PRC
• Budget UCBL : 180 k€

The WHO has designated Respiratory Syncytial Virus (hRSV) and metapneumovirus (hMPV), as a high priority targets for vaccine development, yet no approved vaccines is presently available against these viruses. Several vaccine strategy are currently under development with 19 on going clinical trials. Of note, 18 candidates out of 19 are only focused against hRSV, despite hMPV being very prevalent in the infant population. Considering the important paediatric medical need and socio-economic issue of these infections, it is crucial to develop a broad-spectrum vaccine to fight both hRSV and hMPV infections. Otherwise, live attenuated virus vaccines are very appropriated to immunize children, however the lack of optimized large-scale cell culture process hinders the industrial development of such required vaccines. More generally, viral production capacity of cell-based processes is still hindered by the limited understanding of the complex interactions between the operating conditions and the biology of infected host producer cells. In this context, the METAVAC-T17 project aims at developing and characterizing an optimized up scalable high-yield DuckCeltTM-T17 cell line-based process for the production of a new paediatric live attenuated hRSV/hMPV multivalent vaccine candidate, readily transferable to vaccine manufacturers. The project is based on an already validated and proprietary live attenuated recombinant hMPV strain (?SH-rC-85473) (METAVAC®, FR1856801, FR185705, FR1902934) that induces efficient neutralizing antibody response and protection of mice against high hMPV challenge, and a new proprietary avian DuckCeltTM-T17 cell line (WO2007077256, WO2010130756), cultivated in suspension and serum-free medium, that efficiently produces high-titre, fully functional recombinant METAVAC®viral particles. For the sake of the project success, three highly complementary and multidisciplinary partners that are internationally recognized in their several respective fields of expertise (molecular engineering of viruses, mucosal immunology, characterization of bio-production process at up to 50L scale and development of pharmaceutical formulation for delivery devices) were aggregated. This project would be achieved by setting up five work packages (WP) that aims: (i) to generate an engineering fully functional hMPV ?SH-rC-85473 virus expressing the exogenous protective pre-fusion stabilized form of the hRSV F fusion protein (WP1); (ii) To characterize by Design of Experiment (DOE) the most suitable operating conditions for a robust up scaling of the DuckCeltTM-T17 cell growth (WP2) and (iii) an optimal production of the multivalent hRSV/hMPV vaccine candidate in 2L-5L bioreactor systems (WP3); (iv) To develop a pharmaceutical formulation in unit-dose system for optimal intranasal delivery of the multivalent vaccine candidate (WP4); and (v) to validate pre-clinically the formulated multivalent vaccine candidate, for its capacity and effectiveness to protect mice against both hMPV and hRSV challenges after immunization by intranasal delivery (final WP5). This project is fully in line with the national research strategy France Europe 2020 (Défi sociétal 4 «Health and well-being”, ERC LS07) and takes part to the priority translational medecine program “from bench to patients” that aims to promote the upholding and development in France of health industry R&D activities. We expect our project to have also important impacts for economy and industry through the development of knowledge and new technologies of high value in manufacturing of vaccines, an area of considerable societal and economic importance. The long-term goal of this project is to supply/out-license to vaccine manufacturers a new paediatric live attenuated hRSV/hMPV multivalent vaccine candidate with an optimized upscalable high-yield DuckCeltTM-T17 cell line-based process for production. In this perspective, a start up (Vaxxel) is being created.

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