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.firstpage4153en_US
dc.citation.journalTitleApplied Microbiology and Biotechnologyen_US
dc.citation.lastpage4165en_US
dc.citation.volumeNumber105en_US
dc.contributor.authorLee, Jungsoonen_US
dc.contributor.authorLiu, Zhuyunen_US
dc.contributor.authorChen, Wen-Hsiangen_US
dc.contributor.authorWei, Junfeien_US
dc.contributor.authorKundu, Rakhien_US
dc.contributor.authorAdhikari, Rakeshen_US
dc.contributor.authorRivera, Joanne Altierien_US
dc.contributor.authorGillespie, Portia M.en_US
dc.contributor.authorStrych, Ulrichen_US
dc.contributor.authorZhan, Binen_US
dc.contributor.authorHotez, Peter J.en_US
dc.contributor.authorBottazzi, Maria Elenaen_US
dc.contributor.orgJames A. Baker III Institute for Public Policyen_US
dc.date.accessioned2021-05-27T18:13:32Zen_US
dc.date.available2021-05-27T18:13:32Zen_US
dc.date.issued2021en_US
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.en_US
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.en_US
dc.identifier.doihttps://doi.org/10.1007/s00253-021-11281-3en_US
dc.identifier.urihttps://hdl.handle.net/1911/110648en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
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.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleProcess development and scale-up optimization of the SARS-CoV-2 receptor binding domain–based vaccine candidate, RBD219-N1C1en_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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