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- Title
An Efficient and Scalable Method for the Production of Immunogenic SARS-CoV-2 Virus-like Particles (VLP) from a Mammalian Suspension Cell Line.
- Authors
Hirschberg, Stefan; Ghazaani, Fatemeh; Ben Amor, Ghada; Pydde, Markus; Nagel, Alexander; Germani, Saveria; Monica, Lara; Schlör, Anja; Bauer, Hannes; Hornung, Jane; Voetz, Michael; Dwai, Yamen; Scheer, Benjamin; Ringel, Frauke; Kamal-Eddin, Omar; Harms, Christoph; Füner, Jonas; Adrian, Lorenz; Pruß, Axel; Schulze-Forster, Kai
- Abstract
The rapid evolution of new SARS-CoV-2 variants poses a continuing threat to human health. Vaccination has become the primary therapeutic intervention. The goal of the current work was the construction of immunogenic virus-like particles (VLPs). Here, we describe a human cell line for cost-efficient and scalable production of immunogenic SARS-CoV-2 VLPs. The modular design of the VLP-production platform facilitates rapid adaptation to new variants. Methods: The N, M-, and E-protein genes were integrated into the genome of Expi293 cells (ExpiVLP_MEN). Subsequently, this cell line was further modified for the constitutive expression of the SARS-CoV-2 spike protein. The resulting cell line (ExpiVLP_SMEN) released SARS-CoV-2 VLP upon exposure to doxycycline. ExpiVLP_SMEN cells were readily adapted for VLP production in a 5 L bioreactor. Purified VLPs were quantified by Western blot, ELISA, and nanoparticle tracking analysis and visualized by electron microscopy. Immunogenicity was tested in mice. Results: The generated VLPs contained all four structural proteins, are within the size range of authentic SARS-CoV-2 virus particles, and reacted strongly and specifically with immunoserum from naturally infected individuals. The VLPs were stable in suspension at 4 °C for at least 10 weeks. Mice immunized with VLPs developed neutralizing antibodies against lentiviruses pseudotyped with the SARS-CoV-2 spike protein. The flexibility of the VLP-production platform was demonstrated by the rapid switch of the spike protein to a new variant of concern (BA.1/Omicron). The present study describes an efficient, scalable, and adaptable production method of immunogenic SARS-CoV-2 VLPs with therapeutic potential.
- Subjects
VIRUS-like particles; CELL lines; CELL suspensions; PRODUCTION methods; SARS-CoV-2
- Publication
Vaccines, 2023, Vol 11, Issue 9, p1469
- ISSN
2076-393X
- Publication type
Article
- DOI
10.3390/vaccines11091469