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Region Hovedstaden - en del af Københavns Universitetshospital

Impact of the isoelectric point of model parvoviruses on viral retention in anion-exchange chromatography

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


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  • Remo Leisi
  • Raphael Wolfisberg
  • Thomas Nowak
  • Oliver Caliaro
  • Andreas Hemmerle
  • Nathan J Roth
  • Carlos Ros
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Anion-exchange chromatography (AEX) is used in the downstream purification of monoclonal antibodies to remove impurities and potential viral contamination based on electrostatic interactions. Although the isoelectric point (pI) of viruses is considered a key factor predicting the virus adsorption to the resin, the precise molecular mechanisms involved remain unclear. To address this question, we compared structurally homologous parvoviruses that only differ in their surface charge distribution. A single charged amino acid substitution on the capsid surface of minute virus of mice (MVM) provoked an increased apparent pI (pIapp ) 6.2 compared to wild-type MVM (pIapp  = 4.5), as determined by chromatofocusing. Despite their radically different pIapp , both viruses displayed the same interaction profile in Mono Q AEX at different pH conditions. In contrast, the closely related canine parvovirus (pIapp  = 5.3) displayed a significantly different interaction at pH 5. The detailed structural analysis of the intricate three-dimensional structure of the capsids suggests that the charge distribution is critical, and more relevant than the pI, in controlling the interaction of a virus with the chromatographic resin. This study contributes to a better understanding of the molecular mechanisms governing virus clearance by AEX, which is crucial to enable robust process design and maximize safety.

TidsskriftBiotechnology and bioengineering
Udgave nummer1
Sider (fra-til)116-129
Antal sider14
StatusUdgivet - jan. 2021
Eksternt udgivetJa

ID: 64648812