Production , purification and preparation of various candidiate vaccines

各种候选疫苗的生产、纯化和制备

• 批准号: 7593790
• 负责人: Joseph Shiloach
• 金额: $ 30.26万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593790
• 关键词: Anthrax Vaccines; Anthrax disease; Antigens; Bacillus anthracis; Bacterial Polysaccharides; Biotechnology; Bioterrorism; Clinical Research; Clinical Trials; Clostridium; Collaborations; Conjugate Vaccines; Development; Diphtheria Toxoid; Drug Formulations; Escherichia coli; Evaluation; Formaldehyde; Malaria; Malaria Vaccines; Methods; National Institute of Allergy and Infectious Disease; National Institute of Child Health and Human Development; Pichia; Preparation; Procedures; Production; Proteins; Pseudomonas aeruginosa toxA protein; Public Health; Recombinants; Scientist; Shigella flexneri; Toxin; Vaccines; Work; aluminum sulfate; anthrax protective factor; capsule; improved; microorganism; novel vaccines; plasmid DNA; transmission process; vaccine development

The Unit continued work on the development of new vaccines against Shigella flexneri and Bacillus anthracis, products are currently in clinical trials. A production and purification procedures for recombinant Pseudomonas aeruginosa exotoxin A was developed and gram quantities of the protein were made. This protein was used for the preparation of a conjugated vaccine by conjugating the protein to the bacterial polysaccharide. A production and purification procedure for obtaining inactivated protective antigen from Bacillus anthracis was established and gram quantities of this protein were made. This anthrax vaccine is being studied by using several different formulations: formaldehyde treated, formaldehyde treated with alum, alum alone, and untreated protein. Additionally, conjugating the protective antigen with the anthrax capsule is currently being prepared for clinical studies. Several proteins were prepared for evaluation as a potential candidate for conjugation, among them recombinant toxin A of Clostridium difficle and recombinant diphtheria toxoid. The Biotechnology Unit also produced large quantities of experimental recombinant malaria transmission blocking vaccine from Pichia pastoris, this work was done in collaboration with the Malaria Vaccine Development Unit of NIAID. The Unit was also involved in improving the production procedure of plasmid DNA, evaluating different host microorganisms. Significant increase in specific production was achieved by replacing the current E. coli production strain with a genetically modified strain.

该部门继续致力于针对福氏志贺氏菌和炭疽杆菌的新型疫苗的开发，产品目前正在进行临床试验。开发了重组铜绿假单胞菌外毒素 A 的生产和纯化程序，并制备了克量的蛋白质。该蛋白质用于通过将该蛋白质与细菌多糖缀合来制备缀合疫苗。建立了从炭疽杆菌中获得灭活保护性抗原的生产和纯化程序，并制备了克量的该蛋白质。正在使用几种不同的配方来研究这种炭疽疫苗：甲醛处理的、用明矾处理的甲醛、单独的明矾和未经处理的蛋白质。此外，目前正在准备将保护性抗原与炭疽胶囊结合进行临床研究。制备了几种蛋白质用于评估作为缀合的潜在候选者，其中包括艰难梭菌的重组毒素 A 和重组白喉类毒素。 生物技术部门还利用毕赤酵母生产了大量实验性重组疟疾传播阻断疫苗，这项工作是与NIAID疟疾疫苗开发部门合作完成的。该单位还参与改进质粒DNA的生产程序，评估不同的宿主微生物。通过用转基因菌株替换当前的大肠杆菌生产菌株，实现了比产量的显着增加。