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Bioreactor production of rVSV-vectored vaccines in Vero cell suspension cultures
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  • Sascha Kiesslich,
  • Gyoung Kim,
  • Chun Fang Shen,
  • Chil-Yong Kang,
  • Amine Kamen
Sascha Kiesslich
McGill University

Corresponding Author:[email protected]

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Gyoung Kim
University of Western Ontario Schulich School of Medicine and Dentistry
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Chun Fang Shen
National Research Council Canada
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Chil-Yong Kang
University of Western Ontario Schulich School of Medicine and Dentistry
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Amine Kamen
McGill University
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Abstract

The Vero cell line is the most used continuous cell line in viral vaccine manufacturing. This adherent cell culture platform requires the use of surfaces to support cell growth, typically roller bottles or microcarriers. We have recently compared the production of rVSV-ZEBOV on Vero cells between microcarrier and fixed-bed bioreactors. However, suspension cultures are considered superior with regards to process scalability. Therefore, we further explore the Vero suspension system for rVSV-vectored vaccine production. Previously, this suspension cell line was only able to be cultivated in a proprietary medium. Here, we expand the adaptation and bioreactor cultivation to a serum-free commercial medium. Following small scale optimization and screening studies, we demonstrate bioreactor productions of highly relevant vaccines and vaccine candidates against Ebola virus disease, HIV and COVID-19 in the Vero suspension system. rVSV-ZEBOV, rVSV-HIV and rVSVInd-msp-SF-Gtc can replicate to high titers in the bioreactor, reaching 3.87 × 107 TCID50/mL, 2.12 × 107 TCID50/mL and 3.59 × 109 TCID50/mL, respectively. Further, we compare cell specific productivities, and the quality of the produced viruses by determining the ratio of total viral particles to infectious viral particles
23 Dec 2020Submitted to Biotechnology and Bioengineering
31 Dec 2020Submission Checks Completed
31 Dec 2020Assigned to Editor
12 Jan 2021Reviewer(s) Assigned
05 Feb 2021Review(s) Completed, Editorial Evaluation Pending
05 Feb 2021Editorial Decision: Revise Major
16 Mar 20211st Revision Received
17 Mar 2021Submission Checks Completed
17 Mar 2021Assigned to Editor
31 Mar 2021Reviewer(s) Assigned
08 Apr 2021Review(s) Completed, Editorial Evaluation Pending
08 Apr 2021Editorial Decision: Accept