title: Utilizing dynamic light scattering as a process analytical technology for protein folding and aggregation monitoring in vaccine manufacturing.
abstract: Protein aggregation is a common challenge in the manufacturing of biological products. It is possible to minimize the extent of aggregation through timely measurement and in-depth characterization of aggregation. In this study, we demonstrated the use of dynamic light scattering (DLS) to monitor inclusion body (IB) solubilization, protein refolding, and aggregation near the production line of a recombinant protein-based vaccine candidate. Our results were in good agreement with those measured by size-exclusion chromatography. DLS was also used to characterize the mechanism of aggregation. As DLS is a quick, nonperturbing technology, it can potentially be used as an at-line process analytical technology to ensure complete IB solubilization and aggregate-free refolding.
authors.affiliation: Bioprocess Research and Development, Sanofi Pasteur, Toronto, Ontario, M2R 3T4, Canada.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yu
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Reid
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Yang
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D008027:Light; D011489:Protein Denaturation; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012542:Scattering, Radiation; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012995:Solubility; D014614:Vaccines, Synthetic / Q000737:chemistry*
chemical_list: D007136:Immunoglobulins; D011993:Recombinant Fusion Proteins; C090698:SP1 antigen; D014614:Vaccines, Synthetic; D012710:Serum Albumin, Bovine
keywords: biopharmaceuticals characterization; light scattering (dynamic); particle sizing; process analytical technology (PAT); protein aggregation; protein folding/refolding; vaccines