Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/138638
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Type: | Journal article |
Title: | An integrated and continuous downstream process for microbial virus-like particle vaccine biomanufacture |
Author: | Gerstweiler, L. Billakanti, J. Bi, J. Middelberg, A.P.J. |
Citation: | Biotechnology and Bioengineering, 2022; 119(8):2122-2133 |
Publisher: | Wiley |
Issue Date: | 2022 |
ISSN: | 0006-3592 1097-0290 |
Statement of Responsibility: | Lukas Gerstweiler, Jagan Billakanti, Jingxiu Bi, Anton P. J. Middelberg |
Abstract: | In this study, we present the first integrated and continuous downstream process for the production of microbial virus‐like particle vaccines. Modular murine polyomavirus major capsid VP1 with integrated J8 antigen was used as a model virus‐like particle vaccine. The integrated continuous downstream process starts with crude cell lysate and consists of a flow‐through chromatography step followed by periodic counter‐current chromatography (PCC) (bind‐elute) using salt‐tolerant mixed‐mode resin and subsequent in‐line assembly. The automated process showed a robust behavior over different inlet feed concentrations ranging from 1.0 to 3.2 mg ml−1 with only minimal adjustments needed, and produced continuously high‐quality virus‐like particles, free of nucleic acids, with constant purity over extended periods of time. The average size remained constant between 44.8 ± 2.3 and 47.2 ± 2.9 nm comparable to literature. The process had an overall product recovery of 88.6% and a process productivity up to 2.56 mg h−1 mlresin−1 in the PCC step, depending on the inlet concentration. Integrating a flow through step with a subsequent PCC step allowed streamlined processing, showing a possible continuous pathway for a wide range of products of interest. |
Keywords: | biomanufacture cont Continuous downstream processing process integration vaccine virus-likeparticle |
Rights: | © 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
DOI: | 10.1002/bit.28118 |
Published version: | http://dx.doi.org/10.1002/bit.28118 |
Appears in Collections: | Chemical Engineering publications |
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hdl_138638.pdf | Published version | 2.59 MB | Adobe PDF | View/Open |
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