Process development and scale-up optimization of the SARS-CoV-2 receptor binding domain–based vaccine candidate, RBD219-N1C1

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dc.citation.firstpage4153
dc.citation.journalTitleApplied Microbiology and Biotechnology
dc.citation.lastpage4165
dc.citation.volumeNumber105
dc.contributor.authorLee, Jungsoon
dc.contributor.authorLiu, Zhuyun
dc.contributor.authorChen, Wen-Hsiang
dc.contributor.authorWei, Junfei
dc.contributor.authorKundu, Rakhi
dc.contributor.authorAdhikari, Rakesh
dc.contributor.authorRivera, Joanne Altieri
dc.contributor.authorGillespie, Portia M.
dc.contributor.authorStrych, Ulrich
dc.contributor.authorZhan, Bin
dc.contributor.authorHotez, Peter J.
dc.contributor.authorBottazzi, Maria Elena
dc.contributor.orgJames A. Baker III Institute for Public Policy
dc.date.accessioned2021-05-27T18:13:32Z
dc.date.available2021-05-27T18:13:32Z
dc.date.issued2021
dc.description.abstractA SARS-CoV-2 RBD219-N1C1 (RBD219-N1C1) recombinant protein antigen formulated on Alhydrogel® has recently been shown to elicit a robust neutralizing antibody response against SARS-CoV-2 pseudovirus in mice. The antigen has been produced under current good manufacturing practices (cGMPs) and is now in clinical testing. Here, we report on process development and scale-up optimization for upstream fermentation and downstream purification of the antigen. This includes production at the 1-L and 5-L scales in the yeast, Pichia pastoris, and the comparison of three different chromatographic purification methods. This culminated in the selection of a process to produce RBD219-N1C1 with a yield of >400 mg per liter of fermentation with >92% purity and >39% target product recovery after purification. In addition, we show the results from analytical studies, including SEC-HPLC, DLS, and an ACE2 receptor binding assay that were performed to characterize the purified proteins to select the best purification process. Finally, we propose an optimized upstream fermentation and downstream purification process that generates quality RBD219-N1C1 protein antigen and is fully scalable at a low cost.
dc.identifier.citationLee, Jungsoon, Liu, Zhuyun, Chen, Wen-Hsiang, et al.. "Process development and scale-up optimization of the SARS-CoV-2 receptor binding domain–based vaccine candidate, RBD219-N1C1." <i>Applied Microbiology and Biotechnology,</i> 105, (2021) Springer Nature: 4153-4165. https://doi.org/10.1007/s00253-021-11281-3.
dc.identifier.doihttps://doi.org/10.1007/s00253-021-11281-3
dc.identifier.urihttps://hdl.handle.net/1911/110648
dc.language.isoeng
dc.publisherSpringer Nature
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleProcess development and scale-up optimization of the SARS-CoV-2 receptor binding domain–based vaccine candidate, RBD219-N1C1
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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