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Bioprocessing of viral vaccines––Introduction
Published in Amine Kamen, Laura Cervera, Bioprocessing of Viral Vaccines, 2023
Cell culture technology is the most effective mode of production of viral vaccines. Primary cell lines such as chick embryo fibroblasts are used in the production of measles and mumps vaccines, whereas human diploid cell lines with limited generations such as Wi-38 and MRC-5 derived human lung fibroblasts are used to produce rubella and varicella vaccines. Vero cell line, a continuous cell line derived from the kidney of the African Green Monkey is used to produce Salk polio, rabies, rotavirus, and influenza vaccines exploiting microcarrier technology to enable industrial scale-up of adherent cell cultures. Other continuous cell lines that have been adapted to suspension cultures include the human embryo kidney cells, HEK293 and the primary embryonic retina cells, PER.C6, two transformed human cell lines, that are used to produce adeno-vectored vaccines currently licensed for immunization against SARS-CoV-2 infections. Madin-Darby Canine Kidney, MDCK, continuous cell line has been used as a preferred host for replication of influenza strains and has been adapted to suspension culture for industrial manufacturing of influenza vaccines. The development of these different cell culture platforms and the regulatory framework associated with their use for manufacturing viral vaccines is discussed in Chapter 4, dedicated to cell lines for viral vaccines production.
Continuous Cell Substrate Considerations
Published in Anthony S. Lubiniecki, Large-Scale Mammalian Cell Culture Technology, 2018
In addition to these safeguards, no evidence of tumorigenicity has been found in human or livestock animal recipients of the products prepared in CCL substrates. Many patients have received inoculations of tissue plasminogen activator, erythropoeitin, factor VIII, soluble CD4, GM-CSF, hepatitis B surface antigen vaccine, and various monoclonal antibodies and other recombinant products of continuous cell lines in clinical trials. For tissue plasminogen activator, large doses of 100 mg per patient or more have been used. At the time of writing over 10 kg of CHO-derived tissue plasminogen activator has been sold since late 1987 for administration to over 100,000 human patients. For recombinant factor VIII, erythropoeitin, and soluble CD4 proteins, chronic administration has been employed. Millions have received polio and rabies vaccines prepared in continuous Vero cells. In addition to this human experience, livestock animals have received annual inoculations of foot-and-mouth virus vaccine prepared in BHK-21 (a highly tumorigenic CCL) for up to 14 years without effect (69). No effects have been reported which might be attributed to oncogenic factors.
A review on ‘sulfonamides’: their chemistry and pharmacological potentials for designing therapeutic drugs in medical science
Published in Journal of Coordination Chemistry, 2023
Wardha Zafar, Sajjad Hussain Sumrra, Abrar Ul Hassan, Zahid Hussain Chohan
Khan et al. [111] reported the preparation and anticancer activity of tosyl sulfonamides (L1-L4) and their divalent zinc complexes (28a-28d) towards kidney fibroblast cells (BHK-21), lung carcinoma cells (H-157) and Vero cell lines (Scheme 28). Vincristine was the reference drug that was used for comparison of anticancer activity. All compounds showed low cytotoxicity at Vero cells while exhibiting significant activity towards BHK-21 and H-157 cancer cells. Vero cells are the normal cells isolated from kidney epithelial cell linings of African green monkeys used as a control to determine the safety. The results of the SAR analysis and anticancer assay indicated that the compounds were effectively cytotoxic with significant IC50 values. These compounds also displayed comparatively low toxic behavior towards Vero cells which can be a positive feature of this study for designing and developing safe and potent drug candidates. Zinc complex 28a showed best results against H-157 and BHK-21 cell lines with IC50 values of 1.8 ± 0.1 and 2.2 ± 0.1 μM, respectively, with 13.7% inhibition of Vero cell lines. All the compounds were also evaluated for their carbonic anhydrase (CA) inhibitory efficiency towards bovine CA II (bCA-II) isozyme. Complexes 28b and 28a were the most potent compounds of the assessed series with IC50 values of 0.58 ± 0.09 and 0.64 ± 0.07 μM, respectively. Their SAR analysis showed that 28b and 28a incorporate isobutyl and methyl substituents, respectively.
Graphene oxide-reinforced pectin/chitosan polyelectrolyte complex scaffolds
Published in Journal of Biomaterials Science, Polymer Edition, 2021
P. R. Sivashankari, K. Krishna Kumar, M. Devendiran, M. Prabaharan
An ideal tissue engineering scaffold should promote cell attachment and proliferation. Cell adhesion on tissue engineering scaffolds is the first step in tissue regeneration since other steps such as cell growth, migration, gene expression and differentiation occur after the cells attach to the scaffolds. Hence, to assess the suitability of PCGO scaffolds for tissue engineering, their ability to attach with Vero cells was analyzed. As shown in Figure 8(B), the PCGO-1 and PCGO-2 scaffolds presented the highest amount of cell attachment when compared to PC and PCGO-3 scaffolds due to their improved hydrophilicity. The increased amount of GO and reduced porosity (64%) could be the reasons for the decreased cell attachment ability of PCGO-3 scaffolds. These results confirm that PCGO scaffolds with 1 wt. % of GO could be an excellent substrate for the attachment of cells.
Optimization of non-detergent treatment for enveloped virus inactivation using the Taguchi design of experimental methodology (DOE)
Published in Preparative Biochemistry and Biotechnology, 2019
Roya Khosravi, Seyed Nezamedin Hosseini, Amin Javidanbardan, Maryam Khatami, Hooman Kaghazian, Seyed Dawood Mousavi Nasab
For evaluating the efficacy of viral clearance methods often a model virus, representing similar infectious viruses in terms of structure, is selected.[11,12,25] Herpes virus, ranging from 150 to 200 nm in diameter with large DNA, is one of the mainly used models for enveloped viruses.[24,26,27] Among various herpes viruses, Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2) are the most common contagious pathogens in humans.[24,26,27] In addition to the model virus, type of cell-line should be specified as well. The Vero cell-line derived from African Green Monkey Fibroblast Cells is one of the standard cell lines which is commonly used for the production of viral vaccines.[28–30] These cells grow in a medium adherent to the bottom of the culture vessel (dependent on the support), and by reaching the optimum cell density, they form confluent monolayers on the surface.[28]