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Adenovirus 5 recovery using nanofiber ion exchange adsorbents

Turnbull, J; Wright, B; Green, NK; Tarrant, R; Roberts, I; Hardick, O; Bracewell, DG; (2019) Adenovirus 5 recovery using nanofiber ion exchange adsorbents. Biotechnology and Bioengineering , 116 (7) pp. 1698-1709. 10.1002/bit.26972. Green open access

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Abstract

Viral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of high quality virus remains a challenge. It is desirable to use the adsorption based chromatographic separations that so effectively underpin therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product means it is necessary to revisit the design of sorbent's morphology and surface chemistry. In this study, the behaviour of a cellulose nanofiber ion exchange sorbent derivatised with quaternary (Q) amine ligands at defined densities is characterised to address this. This material was selected as it has a large accessible surface area for viral particles and rapid process times. Initially the impact of surface chemistry on infective product recovery using low (440 µmol/g), medium (750 µmol/g) and high (1029 µmol/g) ligand densities is studied. At higher densities product stability is reduced, this effect increased with prolonged adsorption durations of 24 minutes with just ~10% loss at low ligand density vs. ~50% at high. This could be mitigated by using a high flowrate to reduce the cycle time to ~1 minute. Next the impact of ligand density on the separation's resolution was evaluated. Key to understanding virus quality is the virus particle: infectious virus particle ratio. It was found this parameter could be manipulated using ligand density and elution strategy. Together this provides a basis for viral vector separations that allows for their typically low titres and labile nature by using high liquid velocity to minimise both load and on-column times while separating key product and process related impurities. This article is protected by copyright. All rights reserved.

Type: Article
Title: Adenovirus 5 recovery using nanofiber ion exchange adsorbents
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/bit.26972
Publisher version: http://doi.org/10.1002/bit.26972
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Nanofibers, anion exchange chromatography, downstream processing, viral vectors
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10071389
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