Aggregation of immunoglobulin G (IgG) is a serious concern that results in immunogenicity in pharmaceutical applications. Removal of the small and soluble aggregates in protein solutions through a simple method remains challenging. Here we show that an aqueous two-phase system (ATPS) can be used for the elimination of soluble aggregates from IgG solution. Polyethylene glycol (PEG) and dextran (DEX) were selected as components of the ATPS. As expected, IgG monomers were partitioned into the top or bottom phases of ATPS. Interestingly, almost all the small and soluble aggregates of IgG were extracted to the interface between top and bottom phases, rather than in the liquid phases. The partitioning of monomers and aggregates of IgG can be attributed to the solubility of these protein states in PEG and DEX. Thus, ATPS using PEG and DEX can be employed for the simple removal method of soluble aggregates from IgG solution.
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http://dx.doi.org/10.1016/j.pep.2019.05.002 | DOI Listing |
Sci Rep
January 2025
Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore (UOL), Lahore, Pakistan.
Highly variable response shown by individuals against mosquito-borne infections suggests that host genetic factors play an important role in determining mosquito-borne disease onset. Therefore, it is necessary to determine the genetic risk of these diseases in specific populations. The current study aimed to determine the percentage of individuals in the general population carrying mosquito-borne disease susceptibility and protection-related variants.
View Article and Find Full Text PDFJ Pharm Sci
January 2025
Laboratory of Functional Molecular Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.
Protein aggregation, a major concern in biopharmaceutical quality control, can be accelerated by various stresses during clinical handling. This study investigated potential aggregation risk factors during dilution process with syringe handling for intravenous administration. Using γ-globulin and IgG solutions as surrogate models of antibody therapeutics, we examined the effects of high sliding speeds and piston operations of the syringe on protein aggregation during saline dilution.
View Article and Find Full Text PDFViruses
January 2025
Laboratory of Infectious Diseases, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
Self-assembling ferritin nanoparticle technology is a widely used vaccine development platform for enhancing the efficacy of subunit vaccines by displaying multiple antigens on nanocages. The dengue virus (DENV) envelope domain III (EDIII) protein, the most promising antigen for DENV, has been applied in vaccine development, and it is essential to evaluate the relative immunogenicity of the EDIII protein and EDIII-conjugated ferritin to show the efficiency of the ferritin delivery system compared with EDIII. In this study, we optimized the conditions for the expression of the EDIII protein in , protein purification, and refolding, and these optimization techniques were applied for the purification of EDIII ferritin nanoparticles.
View Article and Find Full Text PDFJ Chromatogr A
January 2025
Center of Molecular Immunology, 216 Street and 15th Avenue Atabey-Siboney Playa P.O. Box 16040, Havana, 11600, Cuba. Electronic address:
Protein A chromatography represents the most prevalent methodology for the capture of monoclonal antibodies. The use of a low pH elution buffer from Protein A has been observed to contribute to product aggregation, particularly in the case of IgG4 antibodies, such as nivolumab. This paper presents a well-defined strategy for addressing this issue.
View Article and Find Full Text PDFAnal Chim Acta
February 2025
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 10591-6707, USA.
Background: The biopharmaceutical industry is increasingly interested in the analysis of trace metals due to their significant impact on product quality and drug safety. Certain metals can potentially accelerate the formation of degradants or aggregates in biotherapeutic proteins, leading to drug product quality concerns. A better understanding of metal-mAb interactions would aid in the development of purification processes and formulations, thereby ensuring better drug quality and safety.
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