Process development for cross-flow diafiltration-based VLP disassembly: A novel high-throughput screening approach.
cross-flow filtration
disassembly
downstream processing
high-throughput screening
virus-like particles
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
09
06
2021
received:
26
03
2021
accepted:
19
06
2021
pubmed:
26
6
2021
medline:
3
3
2022
entrez:
25
6
2021
Statut:
ppublish
Résumé
Virus-like particles (VLPs) are particulate structures, which are applied as vaccines or delivery vehicles. VLPs assemble from subunits, named capsomeres, composed of recombinantly expressed viral structural proteins. During downstream processing, in vivo-assembled VLPs are typically dis- and reassembled to remove encapsulated impurities and to improve particle morphology. Disassembly is achieved in a high-pH solution and by the addition of a denaturant or reducing agent. The optimal disassembly conditions depend on the VLP amino acid sequence and structure, thus requiring material-consuming disassembly experiments. To this end, we developed a low-volume and high-resolution disassembly screening that provides time-resolved insight into the VLP disassembly progress. In this study, two variants of C-terminally truncated hepatitis B core antigen were investigated showing different disassembly behaviors. For both VLPs, the best capsomere yield was achieved at moderately high urea concentration and pH. Nonetheless, their disassembly behaviors differed particularly with respect to disassembly rate and aggregation. Based on the high-throughput screening results, a diafiltration-based disassembly process step was developed. Compared with mixing-based disassembly, it resulted in higher yields of up to 0.84 and allowed for integrated purification. This process step was embedded in a filtration-based process sequence of disassembly, capsomere separation, and reassembly, considerably reducing high-molecular-weight species.
Substances chimiques
Capsid Proteins
0
Hepatitis B Vaccines
0
Vaccines, Virus-Like Particle
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3926-3940Informations de copyright
© 2021 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.
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