Bioreactor production of rVSV‐based vectors in Vero cell suspension cultures

Kießlich, Sascha; Kim, Gyoung Nyoun; Shen, Chun Fang; Kang, C. Yong; Kamen, Amine

doi:10.1002/bit.27785

Cited by 24 publications

(22 citation statements)

References 23 publications

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“…Our results are in agreement with previous studies conducted by Elahi et al ( 2019 ) and Gélinas et al ( 2019 ) showing that shifting to 34°C (from 37°C) led to a threefold or sixfold increase in virus titer. In addition, the production of a VSV‐based Ebola vaccine showed a preference for production at 34°C (Gélinas et al, 2019 , 2020 ; Kiesslich et al, 2021 ). These results led us to test an additional lower temperature value of 31°C.…”

Section: Resultsmentioning

confidence: 99%

“…Production of various VSV‐based vaccines in Vero cells has been reported. However, all reported processes were either in microcarriers (Kiesslich et al, 2020; Mangion et al, 2020) or in cell suspension (Kiesslich et al, 2021) and none were reported in a Fibra‐Cel based production process. Before optimizing the process parameters in the Ambr15 system, a preliminary study was conducted (Jayson et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

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

Rosen

Jayson

Goldvaser

et al. 2022

Biotech & Bioengineering

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Rosen

Jayson

Goldvaser

et al. 2022

Biotech & Bioengineering

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“…Sousa et al [ 14 ] developed a scalable bioprocess for Peste des Petites Ruminants virus (PPRV) vaccine production in Vero cells using SFM, microcarrier technology in STB, in-situ cell detachment from microcarriers and perfusion. Recently, Vero cells have been successfully adapted to grow in suspension in serum-free media [ 15 , 16 ]. Fujii et al [ 17 ] fabricated an ultrasonic irradiation system and used CHO cells as a model example, and they found the culture time was reduced by 14% when the cell number increased 1000-fold.…”

Section: Introductionmentioning

confidence: 99%

Large-Scale Microcarrier Culture of Chinese Perch Brain Cell for Viral Vaccine Production in a Stirred Bioreactor

Luo

Niu

et al. 2021

Vaccines

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Mandarin fish (Siniperca chuatsi) is one of the important cultured fish species in China. Infectious spleen and kidney necrosis virus (ISKNV) and Siniperca Chuatsi rhabdovirus (SCRV) have hindered the development of mandarin fish farming industry. Vaccination is the most effective method for control of viral diseases, however viral vaccine production requires the large-scale culture of cells. Herein, a suspension culture system of Chinese perch brain cell (CPB) was developed on Cytodex 1 microcarrier in a stirred bioreactor. Firstly, CPB cells were cultured using Cytodex 1 microcarrier in 125 mL stirring flasks. With the optimum operational parameters, CPB cells grew well, distributed uniformly, and could fully cover the microcarriers. Then, CPB cells were digested with trypsin and expanded step-by-step with different expansion ratios from the 125 mL stirring bottle to a 500 mL stirring bottle, and finally to a 3-L bioreactor. Results showed that with an expansion ratio of 1:3, we achieved a high cell density level (2.25 × 106 cells/mL) with an efficient use of the microcarriers, which also confirmed the data obtained from the 125 mL stirring flask. Moreover, obvious cytopathic effects (CPE) were observed in the suspended CPB cells post-infection with ISKNV and SCRV. This study provided a large-scale culture system of CPB cells for virus vaccine production.

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“…VERO cells are derived from African green monkey kidney and act as hosts for ERV and SARS-CoV-2, which is a good model for this study. VERO cells are also widely used in the study of the molecular mechanism of virus infection, as well as the production of vaccines and recombinant proteins, and are regarded as an ideal cell model for cultivating influenza vaccines and studying the molecular mechanism of virus infection [ 60 , 61 , 62 ]. VERO cells could not secrete interferon α/β when infected with a virus because of their inherent genetic defects.…”

Section: Discussionmentioning

confidence: 99%

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

Guo

Yang

Liu

et al. 2022

Viruses

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Background. Interferon is a marker of host antiviral immunity, which is disordered in COVID-19 patients. ERV can affect the secretion of interferon through the cGAS-STING pathway. In this study, we explored whether IFN-I and HERV-K (HML-2) were activated in COVID-19 patients and whether there was an interaction between them. Methods. We collected blood samples from COVID-19 patients and healthy controls. We first detected the expression of HERV-K (HML-2) gag, env, and pol genes and IFN-I-related genes between patients and healthy people by qPCR, synchronously detected VERO cells infected with SARS-CoV-2. Then, the chromosome distributions of highly expressed HERV-K (HML-2) gag, env, and pol genes were mapped by the next-generation sequencing results, and GO analysis was performed on the related genes. Results. We found that the HERV-K (HML-2) gag, env, and pol genes were highly expressed in COVID-19 patients and VERO cells infected with SARS-CoV-2. The interferon-related genes IFNB1, ISG15, and IFIT1 were also activated in COVID-19 patients, and GO analysis showed that HERV-K (HML-2) can regulate the secretion of interferon. Conclusions. The high expression of HERV-K (HML-2) might activate the increase of interferon in COVID-19 patients, proving that HERV-K does not only play a negative role in the human body.

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Bioreactor production of rVSV‐based vectors in Vero cell suspension cultures

Cited by 24 publications

References 23 publications

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

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

Large-Scale Microcarrier Culture of Chinese Perch Brain Cell for Viral Vaccine Production in a Stirred Bioreactor

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

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