June 12 – 17, 2022
The emergence of new influenza strains demands the continued development of novel, flexible, and scalable platforms for vaccine production. In this study, we describe advancements in the manufacturing process of influenza hemagglutinin (HA)-displaying virus-like particle (VLP)-based vaccines produced by insect cells, from upstream and downstream processing to analytics and formulation.
Aiming to improve influenza HA-VLPs production, evolutionary engineering and process intensification have been applied. Adaptation of stable Sf-9 cells producing HA-VLPs to hypothermic growth resulted in up to 12-fold higher expression. Likewise, adaptation of parental High Five cells to neutral pH induced a 3-fold higher specific HA-VLPs production rate following infection with baculovirus. In both case studies, the adaptation process had no impact on VLPs activity and morphology. Noteworthy, stable adapted Sf-9 cells could be cultured in perfusion (up to 100x106 cell/mL) and continuous (~20x106 cell/mL) operation modes with cell-specific productivity similar to batch mode.
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António Roldão, Ricardo Correia, Bárbara Fernandes, Sofia B. Carvalho, Ricardo J. S. Silva, and Cristina Peixoto, "Advances in bioprocessing, analytics and formulation of influenza HA-VLP vaccine candidates produced by insect cells" in "Vaccine Technology VIII", Tarit Mukhopadhyay, Merck Research Laboratories, USA; Charles Lutsch, Sanofi Pasteur, France; Linda Hwee-Lin Lua, University of Queensland, Australia; Francesc Godia, Universitat Autònoma de Barcelona, Spain Eds, ECI Symposium Series, (2022). https://dc.engconfintl.org/vaccine_viii/29