Virus Harvesting and Affinity-Based Liquid Chromatography

O'Neil, P F; Balkovic, Edward S.

doi:10.1038/nbt0293-173

Cited by 21 publications

(14 citation statements)

References 12 publications

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“…To increase the capacity of the C75-MA and heparin-MA three 75 cm 2 units were serially combined to obtain an overall adsorption area of 225 cm 2 . Viruses have been shown to bind sulfated polysaccharides such as dextran sulfate, heparin, and heparan sulfate (Lycke et al, 1991;Mitsuya et al, 1988;O'Keeffe et al, 1999;O'Neil and Balkovic, 1993;Opitz et al, 2009). Here, a significant difference in the dynamic binding capacities for the tested heparin and sulfated cellulose matrices was observed.…”

Section: Separation Of Mva-bnmentioning

confidence: 98%

“…Several studies reported antiviral activities of sulfated cellulose and sulfated dextran/dextrines (Baba et al, 1988;Chattopadhyay et al, 2008;Mitsuya et al, 1988;Piret et al, 2000) as well as the binding of virus particles to Cellufine 1 sulfate (O'Neil and Balkovic, 1993;Opitz et al, 2009). Although the precise interaction between these viruses and sulfated cellulose is currently not fully understood, it represents a potential alternative to heparin and heparan sulfate as ligand for MVA-BN 1 virus particles.…”

Section: Introductionmentioning

confidence: 93%

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Capturing of cell culture‐derived modified Vaccinia Ankara virus by ion exchange and pseudo‐affinity membrane adsorbers

Wolff

Siewert

Lehmann

et al. 2009

Biotech & Bioengineering

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Smallpox is an acute, highly infectious viral disease unique to humans, and responsible for an estimated 300-500 million deaths in the 20th century. Following successful vaccination campaigns through the 19th and 20th centuries, smallpox was declared eradicated by the World Health Organization in 1980. However, the threat of using smallpox as a biological weapon prompted efforts of some governments to produce smallpox vaccines for emergency preparedness. An additional aspect for the interest in smallpox virus is its potential use as a platform technology for vector vaccines. In particular, the latter requires a high safety level for routine applications. IMVAMUNE, a third generation smallpox vaccine based on the attenuated Modified Vaccinia Ankara (MVA) virus, demonstrates superior safety compared to earlier generations and represents therefore an interesting choice as viral vector. Current downstream production processes of Vaccinia virus and MVA are mainly based on labor-intensive centrifugation and filtration methods, requiring expensive nuclease treatment in order to achieve sufficient low host-cell DNA levels for human vaccines. This study compares different ion exchange and pseudo-affinity membrane adsorbers (MA) to capture chicken embryo fibroblast cell-derived MVA-BN after cell homogenization and clarification. In parallel, the overall performance of classical bead-based resin chromatography (Cellufine sulfate and Toyopearl AF-Heparin) was investigated. The two tested pseudo-affinity MA (i.e., sulfated cellulose and heparin) were superior over the applied ion exchange MA in terms of virus yield and contaminant depletion. Furthermore, studies confirmed an expected increase in productivity resulting from the increased volume throughput of MA compared to classical bead-based column chromatography methods. Overall virus recovery was approximately 60% for both pseudo-affinity MA and the Cellufine sulfate resin. Depletion of total protein ranged between 86% and 102% for all tested matrices. Remaining dsDNA in the product fraction varied between 24% and 7% for the pseudo-affinity chromatography materials. Cellufine sulfate and the reinforced sulfated cellulose MA achieved the lowest dsDNA product contamination. Finally, by a combination of pseudo-affinity with anion exchange MA a further reduction of host-cell DNA was achieved.

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Section: Separation Of Mva-bnmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 93%

Capturing of cell culture‐derived modified Vaccinia Ankara virus by ion exchange and pseudo‐affinity membrane adsorbers

Wolff

Siewert

Lehmann

et al. 2009

Biotech & Bioengineering

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“…As these cellulose beads contain a low concentration of sulfate esters, the charge density of Cellufine 1 sulfate is lower compared to commonly used ion exchangers. Thus, adsorption of a wide range of viruses is caused by pseudo-affinity binding rather than electrostatic adsorption (O'Neil and Balkovic, 1993).…”

Section: Introductionmentioning

confidence: 99%

Sulfated membrane adsorbers for economic pseudo‐affinity capture of influenza virus particles

Opitz

Lehmann

Reichl

et al. 2009

Biotech & Bioengineering

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Strategies to control outbreaks of influenza, a contagious respiratory tract disease, are focused mainly on prophylactic vaccinations in conjunction with antiviral medications. Currently, several mammalian cell culture-based influenza vaccine production processes are being established, such as the technologies introduced by Novartis Behring (Optaflu) or Baxter International Inc. (Celvapan). Downstream processing of influenza virus vaccines from cell culture supernatant can be performed by adsorbing virions onto sulfated column chromatography beads, such as Cellufine sulfate. This study focused on the development of a sulfated cellulose membrane (SCM) chromatography unit operation to capture cell culture-derived influenza viruses. The advantages of the novel method were demonstrated for the Madin Darby canine kidney (MDCK) cell-derived influenza virus A/Puerto Rico/8/34 (H1N1). Furthermore, the SCM-adsorbers were compared directly to column-based Cellufine sulfate and commercially available cation-exchange membrane adsorbers. Sulfated cellulose membrane adsorbers showed high viral product recoveries. In addition, the SCM-capture step resulted in a higher reduction of dsDNA compared to the tested cation-exchange membrane adsorbers. The productivity of the SCM-based unit operation could be significantly improved by a 30-fold increase in volumetric flow rate during adsorption compared to the bead-based capture method. The higher flow rate even further reduced the level of contaminating dsDNA by about twofold. The reproducibility and general applicability of the developed unit operation were demonstrated for two further MDCK cell-derived influenza virus strains: A/Wisconsin/67/2005 (H3N2) and B/Malaysia/2506/2004. Overall, SCM-adsorbers represent a powerful and economically favorable alternative for influenza virus capture over conventional methods using Cellufine sulfate.

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“…Among other techniques used to recover adenoviral vectors are some chromatographic types, including size-exclusion chromatography (28), affinity chromatography (29), and anion-exchange chromatography (30). These techniques are almost limited because they commonly fail to discriminate the infective particles and contaminants such as noninfective particles and particle components.…”

Section: Polymer/ Saltmentioning

confidence: 99%

Aqueous Two‐Phase Systems (ATPSs) for Extraction and Purification of Biomolecules and Bioparticles

Marques

Molino

Mazzola

et al. 2013

Encyclopedia of Industrial Biotechnology

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The study of biomolecules and bioparticles has achieved great advances, thus increasing the productivity with upstream improvements. Nowadays, downstream processes are the bottleneck in the production of some biopharmaceuticals, a change from the previous years' scene. Current purification platforms will reach their physical limits at some point, creating the necessity for new approaches. This article reviews an alternative method for the extraction and purification of biomolecules/bioparticles denominated as aqueous two‐phase systems (ATPSs) . Biocompatibility and readiness to scale up are some of the characteristics of ATPSs and we also discuss its application in the biotechnology field.

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Virus Harvesting and Affinity-Based Liquid Chromatography

Cited by 21 publications

References 12 publications

Capturing of cell culture‐derived modified Vaccinia Ankara virus by ion exchange and pseudo‐affinity membrane adsorbers

Capturing of cell culture‐derived modified Vaccinia Ankara virus by ion exchange and pseudo‐affinity membrane adsorbers

Sulfated membrane adsorbers for economic pseudo‐affinity capture of influenza virus particles

Aqueous Two‐Phase Systems (ATPSs) for Extraction and Purification of Biomolecules and Bioparticles

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