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In an effort to control and eventually eliminate malaria, the development of transmission-blocking vaccines has long been sought. However, few antigens have been evaluated in clinical trials, often due to limitations in the expression and purification of the antigen in sufficient yield and quality. Pfs230, a surface antigen of gametocytes, has recently advanced to clinical evaluation as a conjugate vaccine using the Pseudomonas aeruginosa exoprotein A carrier protein. Here we continue to build upon prior work of developing a Pfs230 candidate in the baculovirus system, Pfs230C1 (aa 443-731), through systematic process development efforts to improve yield and purity. Various insect cells including High Five, Sf9 and Super Sf9 were first evaluated for quality and quantity of antigen, along with three insect cell media. In the selection of Sf9 cells, an intact Pfs230C1 was expressed and harvested at 48 h for downstream development. A downstream process, utilizing immobilized metal affinity column (IMAC), followed by ion exchange (IEX) membranes (Mustang S) and finally IEX chromatography (DEAE) yielded a pure Pfs230C1 protein. The complete process was repeated three times at the 20 L scale. To support the eventual chemistry manufacturing and controls (CMC) of Pfs230C1, analytical tools, including monoclonal antibodies, were developed to characterize the identity, integrity, and purity of Pfs230C1. These analytical tools, taken in combination with the optimized process, were implemented with Current Good Manufacturing Practices (cGMP) in mind with the ultimate objective of Phase I clinical trials.
This article was published in the following journal.
Name: Protein expression and purification
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A combined vaccine used to prevent infection with diphtheria and tetanus toxoid. This is used in place of DTP vaccine (DIPHTHERIA-TETANUS-PERTUSSIS VACCINE) when PERTUSSIS VACCINE is contraindicated.
A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed)
A bacterial vaccine for the prevention of brucellosis in man and animal. Brucella abortus vaccine is used for the immunization of cattle, sheep, and goats.
A transcription factor characterized by N-terminal and C-terminal CYS2-HIS2 ZINC FINGERS separated by a homeobox. It represses the expression of E-CADHERIN to induce the EPITHELIAL-MESENCHYMAL TRANSITION. It also represses PROTO-ONCOGENE PROTEINS C-BCL-6; regulates the cell type-specific expression of SODIUM-POTASSIUM-EXCHANGING ATPASE; and promotes neuronal differentiation.
A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had mumps or been immunized with live mumps vaccine. Children are usually immunized with measles-mumps-rubella combination vaccine.
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Clinical trials are a set of procedures in medical research conducted to allow safety (or more specifically, information about adverse drug reactions and adverse effects of other treatments) and efficacy data to be collected for health interventions (e.g...