PERTUSSIS TOXIN--AN APPROACH TO A NEW PERTUSSIS VACCINE

百日咳毒素——新型百日咳疫苗的开发方法

• 批准号: 4693835
• 负责人: R D SEKURA
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 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/4693835
• 关键词: Bordetella pertussis; active immunization; antibody neutralization test; attenuated microorganism; bacterial toxins; bactericidal immunity; biotechnology; enzyme linked immunosorbent assay; immunological substance; microorganism culture; pertussis; pertussis vaccine; tissue /cell culture

The incidence of pertussis has been controlled by use of our current whole cell pertussis vaccines. Recent advances in identification of pertussis toxin (PT) as a major protective antigen against pertussis affords and opportunity to produce a new vaccine with improved safety and efficacy. Project Z01 HD 01302 is directed at characterizing the biochemical action of PT; the current project concentrates on development of mnethods for production of PT, as well as methods for neutralization of toxic action and assessing the immune response to toxins thus neutralized. Growth conditions and purification methods scale production of PT under conditions that are suitable for human usage. B. pertussis cultivated in a 100 1 fermentator, yields more than 200 mg of purified PT. This level of PT production makes practical the preparations of experimental vaccines in sufficient quantities to permit clinical trail. Assay methods for monitoring the toxicity and neutralization of toxicity of experimental vaccine preparation have been established. In addition, methods have been established to monitor the retained antigenicity of toxoided PT preparations, and to monitor immue response to PT-toxoids in mice, monkeys, and humans, and also to measure vaccine efficacy in mice and tissue culture. Experimental pertussis vaccines have been developed which show only minimal levels of residual toxic activities, while antigenic activity is only partially reduced. Experimental vaccines prepared by absorption of pertussis toxoid onto aluminum hydroxide are highly antigenic and elicit a PT specific immune response. Immunization with this pertussis toxoid protects mice against both bacterial and toxin challenge, elicits serum antibodies which neutralizes PT in the CHO cell assay. These data predict that this pertussis toxoid will be effective in the prevention of pertussis.

百日咳的发病率已经通过使用我们目前的 细胞百日咳疫苗。百日咳的鉴定研究进展 百日咳毒素(PT)作为百日咳的主要保护性抗原 有机会生产一种安全性和有效性更高的新疫苗。 项目Z01 HD 01302旨在表征生化作用 目前的项目集中在开发用于 PT的生产，以及中和毒性作用和 评估对毒素的免疫反应，从而中和。生长 PT规模化生产的条件及提纯方法 适合人类使用的东西。百日咳百日咳100%培养 发酵罐，可生产200毫克以上的精制PT。这一级别的PT 生产使实验疫苗的制备变得实用 足够的数量允许临床试验。几种常用的检测方法 实验动物的毒性监测及毒性中和 疫苗的准备工作已经确定。此外，方法已经被 建立监测毒素PT残留抗原性的方法 并监测小鼠、猴、小鼠对PT类毒素的免疫应答。 也是为了测量疫苗在老鼠和组织中的效力 文化。百日咳疫苗试验性研究表明， 只有最低水平的残留毒性活性，而抗原性活性 只是部分减少了。吸收法制备实验疫苗 氢氧化铝表面的百日咳类毒素具有很强的抗原性，可诱导 PT特异性免疫反应。百日咳类毒素免疫试验 保护小鼠免受细菌和毒素的攻击，引发血清 在CHO细胞检测中中和PT的抗体。这些数据预示着 这种百日咳类毒素对预防百日咳有效。