ACELLULAR VACCINES AGAINST BACTERIAL PATHOGENS

针对细菌病原体的无细胞疫苗

• 批准号: 3071049
• 负责人: Joseph T Barbieri
• 金额: $ 6.8万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3071049
• 关键词: ADP ribosylation; Bordetella pertussis; G protein; drug design /synthesis /production; laboratory mouse; laboratory rabbit; nucleic acid sequence; pertussis; pertussis toxin; pertussis vaccine; protein structure function; proteolysis

The immediate goal of this research is to construct an effective, nontoxic acellular vaccine against infection by Bordetella pertussis. Pertussis toxin is an extracellular protein produced by B. Pertussis that is both a determinant of virulence and an antigen that elicits protective immunity. Conditions will be established to produce a toxoid of pertussis toxin that lacks cytotoxicity but retains immunogenicity. The genetically engineered toxoid of pertussis toxin will be tested alone and with other antigens of B. pertussis as acellular vaccine candidates. The long-term goals are to develop strategies for the construction of an acellular vaccine against B. pertussis that are applicable for the generation of recombinant DNA-derived acellular vaccines against other bacterial !pathogens. The research project described will define the catalytic properties of the Sl subunit of pertussis toxin. The aim is to define the function of specific residues within the Sl subunit that reduce toxicity but retain immunogenicity. This research will also focus on determining the mechanism of action of pertussis toxin by defining how pertussis toxin is activated, enters sensitive cells, and interacts with G-proteins.

本研究的直接目标是构建一个有效的， 抗百日咳杆菌感染的无毒无细胞疫苗。 百日咳毒素是由B产生的细胞外蛋白。百日咳， 是毒力决定因素和增强保护性的抗原 免疫力 将建立产生以下类毒素的条件 百日咳毒素缺乏细胞毒性，但保留免疫原性。 的 将单独测试百日咳毒素的基因工程类毒素， 与B的其他抗原结合。百日咳疫苗作为无细胞疫苗的候选者。 的 长期目标是制定战略， 抗B的无细胞疫苗。百日咳疫苗，适用于 产生针对其它病毒的重组DNA衍生的无细胞疫苗 细菌！病原体 所描述的研究项目将定义催化性能的 百日咳毒素S1亚单位。 其目的是确定 S1亚单位内的特定残基，其降低毒性但保留 免疫原性 这项研究还将侧重于确定 通过定义百日咳毒素是如何 被激活，进入敏感细胞，并与G蛋白相互作用。