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Scalable, methanol-free manufacturing of the SARS-CoV-2 receptor-binding domain in engineered Komagataella phaffii.
Dalvie, Neil C; Biedermann, Andrew M; Rodriguez-Aponte, Sergio A; Naranjo, Christopher A; Rao, Harish D; Rajurkar, Meghraj P; Lothe, Rakesh R; Shaligram, Umesh S; Johnston, Ryan S; Crowell, Laura E; Castelino, Seraphin; Tracey, Mary K; Whittaker, Charles A; Love, J Christopher.
  • Dalvie NC; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Biedermann AM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Rodriguez-Aponte SA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Naranjo CA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Rao HD; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Rajurkar MP; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Lothe RR; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Shaligram US; Serum Institute of India Pvt. Ltd., Pune, India.
  • Johnston RS; Serum Institute of India Pvt. Ltd., Pune, India.
  • Crowell LE; Serum Institute of India Pvt. Ltd., Pune, India.
  • Castelino S; Serum Institute of India Pvt. Ltd., Pune, India.
  • Tracey MK; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Whittaker CA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • Love JC; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Biotechnol Bioeng ; 119(2): 657-662, 2022 02.
Article in English | MEDLINE | ID: covidwho-1516721
Preprint
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ABSTRACT
Prevention of COVID-19 on a global scale will require the continued development of high-volume, low-cost platforms for the manufacturing of vaccines to supply ongoing demand. Vaccine candidates based on recombinant protein subunits remain important because they can be manufactured at low costs in existing large-scale production facilities that use microbial hosts like Komagataella phaffii (Pichia pastoris). Here, we report an improved and scalable manufacturing approach for the SARS-CoV-2 spike protein receptor-binding domain (RBD); this protein is a key antigen for several reported vaccine candidates. We genetically engineered a manufacturing strain of K. phaffii to obviate the requirement for methanol induction of the recombinant gene. Methanol-free production improved the secreted titer of the RBD protein by >5X by alleviating protein folding stress. Removal of methanol from the production process enabled to scale up to a 1200 L pre-existing production facility. This engineered strain is now used to produce an RBD-based vaccine antigen that is currently in clinical trials and could be used to produce other variants of RBD as needed for future vaccines.
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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines / Variants Language: English Journal: Biotechnol Bioeng Year: 2022 Document Type: Article Affiliation country: Bit.27979

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines / Variants Language: English Journal: Biotechnol Bioeng Year: 2022 Document Type: Article Affiliation country: Bit.27979