Publication Details |
Category | Text Publication |
Reference Category | Journals |
DOI | 10.3390/vaccines11091469 |
Licence | |
Title (Primary) | An efficient and scalable method for the production of immunogenic SARS-CoV-2 virus-like particles (VLP) from a mammalian suspension cell line |
Author | Hirschberg, S.; Ghazaani, F.; Ben Amor, G.; Pydde, M.; Nagel, A.; Germani, S.; Monica, L.; Schlör, A.; Bauer, H.; Hornung, J.; Voetz, M.; Dwai, Y.; Scheer, B.; Ringel, F.; Kamal-Eddin, O.; Harms, C.; Füner, J.; Adrian, L.; Pruß, A.; Schulze-Forster, K.; Hanack, K.; Kamhieh-Milz, J. |
Source Titel | Vaccines |
Year | 2023 |
Department | UBT |
Volume | 11 |
Issue | 9 |
Page From | art. 1469 |
Language | englisch |
Topic | T7 Bioeconomy |
Supplements | https://www.mdpi.com/article/10.3390/vaccines11091469/s1 |
Keywords | virus-like particle (VLP); SARS-CoV-2; vaccine; stable cell line; neutralizing antibodies |
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. |
Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=27948 |
Hirschberg, S., Ghazaani, F., Ben Amor, G., Pydde, M., Nagel, A., Germani, S., Monica, L., Schlör, A., Bauer, H., Hornung, J., Voetz, M., Dwai, Y., Scheer, B., Ringel, F., Kamal-Eddin, O., Harms, C., Füner, J., Adrian, L., Pruß, A., Schulze-Forster, K., Hanack, K., Kamhieh-Milz, J. (2023): An efficient and scalable method for the production of immunogenic SARS-CoV-2 virus-like particles (VLP) from a mammalian suspension cell line Vaccines 11 (9), art. 1469 10.3390/vaccines11091469 |