Development of suspension adapted Vero cell culture process technology for production of viral vaccines

Shen, Chun Fang; Guilbault, Claire; Li, Xiuling; Elahi, Seyyed Mehdy; Ansorge, Sven; Kamen, Amine; Gilbert, Rénald

doi:10.1016/j.vaccine.2019.07.003

Cited by 56 publications

(70 citation statements)

References 16 publications

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“…In a previous study, Vero cells adapted to suspension growth showed a 1.5-fold efficacy for VSV propagation [14]. Another study demonstrated that suspension-adapted Vero cells produced 3-fold higher amounts of viruses than adherent Vero cells [7]. In this study, we showed that Vero cells cultured in shaking suspension culture system generated 1.5-fold higher amounts of adenovirus than the Vero cells cultured in adhesive plate.…”

Section: Discussionsupporting

confidence: 53%

“…Rourou et al [6] reported that suspension cultivation of agitated Vero cell cultures promoted measles and rabies virus production from these cells. In addition, Shen et al [7] showed that suspension-adapted Vero cells cultivated without microcarriers produced higher amounts of vesicular stomatitis virus (VSV) than adherent Vero cells. However, some hurdles associated with Vero cells, such as longer cell doubling time and low cell viability, still remain to be addressed via the formulation of appropriate adaptation processes.…”

mentioning

confidence: 99%

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Suspension culture of Vero cells for the production of adenovirus type 5

Lee

Park

Seo

2020

Clin Exp Vaccine Res

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Section: Discussionsupporting

confidence: 53%

mentioning

confidence: 99%

Suspension culture of Vero cells for the production of adenovirus type 5

Lee

Park

Seo

2020

Clin Exp Vaccine Res

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“…Vero cells are extensively used for virus propagation 38 including HSV. In the present study, we performed the Vero cells sensitivity against HSV-1 infection.…”

Section: Discussionmentioning

confidence: 99%

Establishment of Simple Cell-based Screening Assay and the Identification of Potent Antiviral Activity of a Plant Extract against HSV-1

Rahmasari¹,

Haruyama²,

Raekiansyah³

et al. 2020

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Herpes simplex virus (HSV) is one of the viruses which cause medical problems in human. 9,10 There are two distinct serotypes of HSV, type 1 (HSV-1) and type 2 (HSV-2). The transmission of HSV-1 through contact with infected lesions or other parts of the body is much easier than HSV-2 which is transmitted through genital contact. It has been reported that the HSV-1 infection rate is two times higher than HSV-2. 9-11 In immunocompromised individuals such as cancer, HIV or organ transplant patients, the clinical manifestation may be more complicated resulting in HSV encephalitis, damage of temporal lobes, pneumonitis, esophagitis, and hepatitis. The HSV-1 infection is also related to the establishment of latent infection in the trigeminal area, where it can be reactivated and cause recurrent ABSTRACT Backgrounds: Drug screening is a time-consuming and costly process confronted with low productivity and challenges in using animals, which limits the discovery of new drugs. The cellbased assay allows the minimization of using the animal models and can provide more relevant in vivo biological information than biochemical assay. Objective: We aimed to establish a simple cell-based screening assay for the discovery of lead extract against HSV-1. Materials and Methods: Assay setting up was performed by optimization of the cell, incubation time, virus titer, and determination of Z value. Results: We have successfully established reproducible methods, by setting up assay plate including determination: 1) Vero cells as a model for HSV-1 infection, 2) Incubation for 5 days as sufficient time for CPE endpoint at monolayer cells, 3) 100 TCID 50 /well HSV-1 as infection titer which caused high percentage of cell detachment, 4) determination of Z value of 100 TCID 50 /well infection > 0.5. In addition, the established system was tested using ACV as the most common anti-HSV drug. Furthermore, we demonstrated the current system to screen extracts from Acacia nilotica, Uncaria gambir and Aspalathus linearis against HSV-1. It was observed that the alkaline extract of Uncaria gambir exhibited the highest SI (12.5) compared to other extracts. Conclusion: We demonstrated current cellbased screening system was reproducible and able to identify lead extracts against HSV-1 infection.

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“…However, this system was not further exploited. A decade later, new efforts were made and two other lab groups described the adaptation of Vero cells to grow in serum-free suspension cultures ( Rourou et al, 2019 ; Shen et al, 2019 ). Shen et al demonstrated the operation of batch and perfusion bioreactors, including biomass monitoring via capacitance, as well as rVSV production in this system.…”

Section: Suspension Culturesmentioning

confidence: 99%

“…Low cell growth rates with doubling times of more than 40 h and the frequent formation of aggregates remain important issues. Media development will certainly play an important role, highlighted by the fact that no commercial media but only in-house media were able to support Vero suspension cultures ( Rourou et al, 2019 ; Shen et al, 2019 ). For example, cell adhesion is heavily dependent on the concentration of the bivalent cation of calcium in the cell surrounding environment and thus media with reduced concentrations could decrease cell aggregation.…”

Section: Suspension Culturesmentioning

confidence: 99%

Vero cell upstream bioprocess development for the production of viral vectors and vaccines

Kießlich

Kamen

2020

Biotechnology Advances

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The Vero cell line is considered the most used continuous cell line for the production of viral vectors and vaccines. Historically, it is the first cell line that was approved by the WHO for the production of human vaccines. Comprehensive experimental data on the production of many viruses using the Vero cell line can be found in the literature. However, the vast majority of these processes is relying on the microcarrier technology. While this system is established for the large-scale manufacturing of viral vaccine, it is still quite complex and labor intensive. Moreover, scale-up remains difficult and is limited by the surface area given by the carriers. To overcome these and other drawbacks and to establish more efficient manufacturing processes, it is a priority to further develop the Vero cell platform by applying novel bioprocess technologies. Especially in times like the current COVID-19 pandemic, advanced and scalable platform technologies could provide more efficient and cost-effective solutions to meet the global vaccine demand. Herein, we review the prevailing literature on Vero cell bioprocess development for the production of viral vectors and vaccines with the aim to assess the recent advances in bioprocess development. We critically underline the need for further research activities and describe bottlenecks to improve the Vero cell platform by taking advantage of recent developments in the cell culture engineering field.

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Development of suspension adapted Vero cell culture process technology for production of viral vaccines

Cited by 56 publications

References 16 publications

Suspension culture of Vero cells for the production of adenovirus type 5

Suspension culture of Vero cells for the production of adenovirus type 5

Establishment of Simple Cell-based Screening Assay and the Identification of Potent Antiviral Activity of a Plant Extract against HSV-1

Vero cell upstream bioprocess development for the production of viral vectors and vaccines

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