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

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          Abstract

          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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          Oncolytic viruses as engineering platforms for combination immunotherapy

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            Is Open Access

            The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line

            Continuous cell lines that originate from mammalian tissues serve as not only invaluable tools for life sciences, but also important animal cell substrates for the production of various types of biological pharmaceuticals. Vero cells are susceptible to various types of microbes and toxins and have widely contributed to not only microbiology, but also the production of vaccines for human use. We here showed the genome landscape of a Vero cell line, in which 25,877 putative protein-coding genes were identified in the 2.97-Gb genome sequence. A homozygous ∼9-Mb deletion on chromosome 12 caused the loss of the type I interferon gene cluster and cyclin-dependent kinase inhibitor genes in Vero cells. In addition, an ∼59-Mb loss of heterozygosity around this deleted region suggested that the homozygosity of the deletion was established by a large-scale conversion. Moreover, a genomic analysis of Vero cells revealed a female Chlorocebus sabaeus origin and proviral variations of the endogenous simian type D retrovirus. These results revealed the genomic basis for the non-tumourigenic permanent Vero cell lineage susceptible to various pathogens and will be useful for generating new sub-lines and developing new tools in the quality control of Vero cells.
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              Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines.

              The development of cell culture systems for virus propagation has led to major advances in virus vaccine development. Primary and diploid cell culture systems are now being replaced by the use of continuous cell lines (CCLs). These substrates are gaining increasing acceptance from regulatory authorities as improved screening technologies remove fears regarding their potential oncogenic properties. The Vero cell line is the most widely accepted CCL by regulatory authorities and has been used for over 30 years for the production of polio and rabies virus vaccines. The recent licensure of a Vero cell-derived live virus vaccine (ACAM2000, smallpox vaccine) has coincided with an explosion in the development of a range of new viral vaccines, ranging from live-attenuated pediatric vaccines against rotavirus infections to inactivated whole-virus vaccines against H5N1 pandemic influenza. These developments have illustrated the value of this cell culture platform in the rapid development of vaccines against a range of virus diseases.
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                Author and article information

                Contributors
                Journal
                Biotechnol Adv
                Biotechnol. Adv
                Biotechnology Advances
                The Authors. Published by Elsevier Inc.
                0734-9750
                1873-1899
                5 August 2020
                15 November 2020
                5 August 2020
                : 44
                : 107608
                Affiliations
                Department of Bioengineering, McGill University, 817 Sherbrooke Street West, Montreal, Quebec H3A 0C3, Canada
                Author notes
                [* ]Corresponding author. amine.kamen@ 123456mcgill.ca
                Article
                S0734-9750(20)30110-5 107608
                10.1016/j.biotechadv.2020.107608
                7405825
                32768520
                85b50801-f950-456c-a847-3ed865a960e7
                © 2020 The Authors

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 24 June 2020
                : 28 July 2020
                : 30 July 2020
                Categories
                Article

                Biotechnology
                vero,cell culture,process development,virus production,optimization,vaccines,bioreactor,microcarrier,suspension culture,ccid, cell culture infectious dose,moi, multiplicity of infection,pat, process analytical technology,pfu, plaque forming units,toh, time of harvest,toi, time of infection

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