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Optimization of VSV-ΔG-spike production process with the Ambr15 system for a SARS-COV-2 vaccine.

Authors
  • Rosen, Osnat1
  • Jayson, Avital1
  • Goldvaser, Michael2
  • Dor, Eyal1
  • Monash, Arik1
  • Levin, Lilach1
  • Cherry, Lilach1
  • Lupu, Edith1
  • Natan, Niva1
  • Girshengorn, Meni1
  • Epstein, Eyal1
  • 1 Department of Biotechnology, Israel Institute for Biological, Chemical and Environmental Sciences, Ness Ziona, Israel. , (Israel)
  • 2 Department of Organic Chemistry, Israel Institute for Biological, Chemical and Environmental Sciences, Ness Ziona, Israel. , (Israel)
Type
Published Article
Journal
Biotechnology and Bioengineering
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jul 01, 2022
Volume
119
Issue
7
Pages
1839–1848
Identifiers
DOI: 10.1002/bit.28088
PMID: 35319097
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To face the coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, our institute has developed the rVSV-ΔG-spike vaccine, in which the glycoprotein of vesicular stomatitis virus (VSV) was replaced by the spike protein of SARS-CoV-2. Many process parameters can influence production yield. To maximize virus vaccine yield, each parameter should be tested independently and in combination with others. Here, we report the optimization of the production of the VSV-ΔG-spike vaccine in Vero cells using the Ambr15 system. This system facilitates high-throughput screening of process parameters, as it contains 24 individually controlled, single-use stirred-tank minireactors. During optimization, critical parameters were tested. Those parameters included: cell densities; the multiplicity of infection; virus production temperature; medium addition and medium exchange; and supplementation of glucose in the virus production step. Virus production temperature, medium addition, and medium exchange were all found to significantly influence the yield. The optimized parameters were tested in the BioBLU 5p bioreactors production process and those that were found to contribute to the vaccine yield were integrated into the final process. The findings of this study demonstrate that an Ambr15 system is an effective tool for bioprocess optimization of vaccine production using macrocarriers and that the combination of production temperature, rate of medium addition, and medium exchange significantly improved virus yield. © 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.

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