Development and optimisation of a procedure for the production of Parapoxvirus ovis by large-scale microcarrier cell culture in a non-animal, non-human and non-plant-derived medium

Pohlscheidt, Michael; Langer, Uwe; Minuth, Torsten; Bödeker, Berthold G. D.; Apeler, Heiner; Hörlein, H.; Paulsen, Daniela; Rübsamen‐Waigmann, Helga; Henzler, Hans‐Jürgen; Reichl, Udo

doi:10.1016/j.vaccine.2008.01.032

Cited by 20 publications

(17 citation statements)

References 43 publications

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“…Parapoxvirus ovis (ORFV) strain NZ2 or D1701 was propagated in bovine kidney cells (BK KL3A) isolated from a fetal calf in 1963 [17]. Briefly, the virus was harvested when approximately 80–90% of the cells showed a cytopathic effect.…”

Section: Methodsmentioning

confidence: 99%

Inactivated Orf Virus Shows Antifibrotic Activity and Inhibits Human Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Replication in Preclinical Models

et al. 2013

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Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

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Section: Methodsmentioning

confidence: 99%

Inactivated Orf Virus Shows Antifibrotic Activity and Inhibits Human Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Replication in Preclinical Models

et al. 2013

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“…Afterward, the remaining volume of the well was filled with a trypsin solution (10 mg/ mL; Invitrogen) up to a final volume of 400 lL and a picture of all settled microcarriers on the bottom of the well was made (10Â final magnification, bright field, AVT Horn 3 CCD camera, Sony; Software Optimas 6.2, Cybernetics). Then, the 96-well plate was incubated at 37 C for 15-20 min. After successful cell detachment (control under the microscope), the cell number in the supernatant was determined using a Fuchs-Rosenthal haemocytometer.…”

Section: Analyticsmentioning

confidence: 99%

Growth behavior of number distributed adherent MDCK cells for optimization in microcarrier cultures

Böck

Sann

Schulze‐Horsel

et al. 2009

Biotechnology Progress

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An assay for measuring the number of adherent cells on microcarriers that is independent from dilution errors in sample preparation was used to investigate attachment dynamics and cell growth. It could be shown that the recovery of seeded cells is a function of the specific rates of cell attachment and cell death, and finally a function of the initial cell-to-bead ratio. An unstructured, segregated population balance model was developed that considers individual classes of microcarriers covered by 1-220 cells/bead. The model describes the distribution of initially attached cells and their growth in a microcarrier system. The model distinguishes between subpopulations of dividing and nondividing cells and describes in a detailed way cell attachment, cell growth, density-dependent growth inhibition, and basic metabolism of Madin-Darby canine kidney cells used in influenza vaccine manufacturing. To obtain a model approach that is suitable for process control applications, a reduced growth model without cell subpopulations, but with a formulation of the specific cell growth rate as a function of the initial cell distribution on microcarriers after seeding was developed. With both model approaches, the fraction of growth-inhibited cells could be predicted. Simulation results of two cultivations with a different number of initially seeded cells showed that the growth kinetics of adherent cells at the given cultivation conditions is mainly determined by the range of disparity in the initial distribution of cells on microcarriers after attachment.

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“…To address this issue, , current strategies include both simple and straightforward processes of fresh medium addition 12 and medium exchanging, and the relatively complex processes like fedbatch and perfusion. [13][14][15][16][17][18][19] In particular, one reported approach utilizes an alternating tangential flow (ATF) system. 18 With eight successful high cell-density ATF perfusion runs for the production of H1N1 virus, it was demonstrated that cell-specific virus yields could be kept constant and cell-specific infectious virus titers were even higher than those of batch cultures (Fig.…”

Section: Current Strategies To Overcome Nutritional Limitationmentioning

confidence: 99%

“…[9][10][11] Not surprisingly, the common maintaining media used in virus production processes cannot provide sufficient nutrients in general and additional supplementation of nutrients must be performed. Currently, several strategies have been exploited to address this issue of nutritional limitation, including fresh medium replenishment, medium-exchanging, fed-batch, perfusion, etc.. [12][13][14][15][16][17][18] However, a rational design of medium supplementation based on comprehensive nutritional analyses for cells during virus production phase is still missing. Only through a detailed analysis on the differences in the cellular metabolism before and after viral infection, an insight understanding of real nutritional requirements during virus production phase can be achieved, and a rational design of medium supplementation can be solid.…”

Section: Introductionmentioning

confidence: 99%

Overcoming nutrient limitations for cell-based production of influenza vaccine

Liu

Ding

Tan

et al. 2015

Human Vaccines & Immunotherapeutics

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Development and optimisation of a procedure for the production of Parapoxvirus ovis by large-scale microcarrier cell culture in a non-animal, non-human and non-plant-derived medium

Cited by 20 publications

References 43 publications

Inactivated Orf Virus Shows Antifibrotic Activity and Inhibits Human Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Replication in Preclinical Models

Inactivated Orf Virus Shows Antifibrotic Activity and Inhibits Human Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Replication in Preclinical Models

Growth behavior of number distributed adherent MDCK cells for optimization in microcarrier cultures

Overcoming nutrient limitations for cell-based production of influenza vaccine

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