Rapid and Scalable Production of Functional SARS-CoV-2 Virus-like Particles (VLPs) by a Stable HEK293 Cell Pool
Name
vaccines-12-00561.pdf
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6.85 MB
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Author(s)
Puarattana-aroonkorn, Sitthiphol
Tharakaraman, Kannan
Suriyawipada, Disapan
Ruchirawat, Mathuros
Fuangthong, Mayuree
Sasisekharan, Ram
Artpradit, Charlermchai
Date Issued
May 21, 2024
Journal
Vaccines
Publisher
MDPI AG
Citation
Puarattana-aroonkorn, S.; Tharakaraman, K.; Suriyawipada, D.; Ruchirawat, M.; Fuangthong, M.; Sasisekharan, R.; Artpradit, C. Rapid and Scalable Production of Functional SARS-CoV-2 Virus-like Particles (VLPs) by a Stable HEK293 Cell Pool. Vaccines 2024, 12, 561.
Version
Final published version
Abstract
At times of pandemics, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation demands rapid development and production timelines of safe and effective vaccines for delivering life-saving medications quickly to patients. Typical biologics production relies on using the lengthy and arduous approach of stable single-cell clones. Here, we used an alternative approach, a stable cell pool that takes only weeks to generate compared to a stable single-cell clone that needs several months to complete. We employed the membrane, envelope, and highly immunogenic spike proteins of SARS-CoV-2 to produce virus-like particles (VLPs) using the HEK293-F cell line as a host system with an economical transfection reagent. The cell pool showed the stability of protein expression for more than one month. We demonstrated that the production of SARS-CoV-2 VLPs using this cell pool was scalable up to a stirred-tank 2 L bioreactor in fed-batch mode. The purified VLPs were properly assembled, and their size was consistent with the authentic virus. Our particles were functional as they specifically entered the cell that naturally expresses ACE-2. Notably, this work reports a practical and cost-effective manufacturing platform for scalable SARS-CoV-2 VLPs production and chromatographic purification.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.3390/vaccines12060561
