Reduced surface area chromatography for flow-through purification of viruses and virus like particles

Iyer, Ganesh; Ramaswamy, Senthilkumar; Asher, Damon R.; Mehta, Ushma; Leahy, Anne; Chung, Franklin; Cheng, Kwok-Shun

doi:10.1016/j.chroma.2011.04.086

Cited by 28 publications

(11 citation statements)

References 25 publications

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“…In particular, new bead‐based resins have been developed for intermediate virus purification and polishing in flow‐through mode. Iyer et al () proposed the increase of the mean bead diameter to maximize the binding capacity for the impurities and reduce the overall column surface available for virus binding. GE Healthcare recently launched Capto Core 700, a resin composed of an active core, functionalized with octylamine ligand, and an inactive porous shell that excludes larger molecules from entering the core, thus allowing them to be collected in the flow‐through.…”

Section: Chromatographymentioning

confidence: 99%

Improved virus purification processes for vaccines and gene therapy

Nestola

Peixoto

Silva

et al. 2015

Biotech & Bioengineering

113

106

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The downstream processing of virus particles for vaccination or gene therapy is becoming a critical bottleneck as upstream titers keep improving. Moreover, the growing pressure to develop cost-efficient processes has brought forward new downstream trains. This review aims at analyzing the state-of-the-art in viral downstream purification processes, encompassing the classical unit operations and their recent developments. Emphasis is given to novel strategies for process intensification, such as continuous or semi-continuous systems based on multicolumn technology, opening up process efficiency. Process understanding in the light of the pharmaceutical quality by design (QbD) initiative is also discussed. Finally, an outlook of the upcoming breakthrough technologies is presented.

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Section: Chromatographymentioning

confidence: 99%

Improved virus purification processes for vaccines and gene therapy

Nestola

Peixoto

Silva

et al. 2015

Biotech & Bioengineering

113

106

View full text Add to dashboard Cite

show abstract

“…The same method was used for intermediate purification of HIV gag‐VLPs [51]. In addition, there is also a tendency to use anion exchange membrane adsorbers for flow‐through purification of large biomolecules [117, 118]. Flow‐through chromatography is especially suitable for the purification of lipid‐enveloped and less stable VLPs because the risk of product alterations by binding and elution is reduced.…”

Section: Downstream Process Unit Operations For Virus‐like Particlesmentioning

confidence: 99%

Next generation vaccines and vectors: Designing downstream processes for recombinant protein‐based virus‐like particles

Effio

Hubbuch

2015

Biotechnology Journal

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In recent years, the development of novel recombinant virus-like particles (VLPs) has been generating new perspectives for the prevention of untreated and arising infectious diseases. However, cost-reduction and acceleration of manufacturing processes for VLP-based vaccines or vectors are key challenges for the global health system. In particular, the design of rapid and cost-efficient purification processes is a critical bottleneck. In this review, we describe and evaluate new concepts, development strategies and unit operations for the downstream processing of VLPs. A special focus is placed on purity requirements and current trends, as well as chances and limitations of novel technologies. The discussed methods and case studies demonstrate the advances and remaining challenges in both rational process development and purification tools for large biomolecules. The potential of a new era of VLP-based products is highlighted by the progress of various VLPs in clinical phases.

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“…Although such a pore size can accommodate most of the proteins, the agarose‐based adsorbent excludes viruses and VLPs due to the diffusional limitation, as the molecular sizes of viruses and VLPs are approximately the same as the pore size of agarose‐based adsorbent . Hence, the majority of VLPs can only be adsorbed on the external surface of the adsorbents , thereby reducing the adsorbent's effective capacity.…”

Section: Introductionmentioning

confidence: 99%

Size‐selective purification of hepatitis B virus‐like particle in flow‐through chromatography: Types of ion exchange adsorbent and grafted polymer architecture

Lee

Chua

et al. 2018

J of Separation Science

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Hepatitis B virus-like particles expressed in Escherichia coli were purified using anion exchange adsorbents grafted with polymer poly(oligo(ethylene glycol) methacrylate) in flow-through chromatography mode. The virus-like particles were selectively excluded, while the relatively smaller sized host cell proteins were absorbed. The exclusion of virus-like particles was governed by the accessibility of binding sites (the size of adsorbents and the charge of grafted dextran chains) as well as the architecture (branch-chain length) of the grafted polymer. The branch-chain length of grafted polymer was altered by changing the type of monomers used. The larger adsorbent (90 μm) had an approximately twofold increase in the flow-through recovery, as compared to the smaller adsorbent (30 μm). Generally, polymer-grafted adsorbents improved the exclusion of the virus-like particles. Overall, the middle branch-chain length polymer grafted on larger adsorbent showed optimal performance at 92% flow-through recovery with a purification factor of 1.53. A comparative study between the adsorbent with dextran grafts and the polymer-grafted adsorbent showed that a better exclusion of virus-like particles was achieved with the absorbent grafted with inert polymer. The grafted polymer was also shown to reduce strong interaction between binding sites and virus-like particles, which preserved the particles' structure.

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Reduced surface area chromatography for flow-through purification of viruses and virus like particles

Cited by 28 publications

References 25 publications

Improved virus purification processes for vaccines and gene therapy

Improved virus purification processes for vaccines and gene therapy

Next generation vaccines and vectors: Designing downstream processes for recombinant protein‐based virus‐like particles

Size‐selective purification of hepatitis B virus‐like particle in flow‐through chromatography: Types of ion exchange adsorbent and grafted polymer architecture

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