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: 3965843
• 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/3965843
• 关键词: Bordetella pertussis; active immunization; antibacterial antibody; antibody neutralization test; bacterial toxins; bactericidal immunity; biotechnology; enzyme linked immunosorbent assay; human subject; human therapy evaluation; human tissue; immunological substance; microorganism culture; pertussis; pertussis vaccine; tissue /cell culture; toxoids

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 an opportunity to produce a new vaccine with improved safety and efficacy. The current project concentrates on development of methods for production of PT, as well as methods for neutralization of toxic action and assessing the immune response to the resultant pertussis toxoid vaccine. Growth conditions and purification methods have been developed to produce PT in the quantities necessary for clinical study. 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 immune response to PT-toxoids in mice, monkeys, and humans, and also to measure vaccine efficacy in mice and tissue culture. Methods have developed to inactivate pertussis toxin and prepare pertussis toxoids. Pertussis toxoids, prepared in our laboratory, 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 and elicits serum antibodies, which neutralizes PT in the CHO cell assay. Immunization of juvenile Rhesus monkeys with the vaccine leads to a similar increase in PT neutralizing antibodies. On the basis of the safety and immunogenicity in animals, a protocol for clinical investigation of the vaccine has been drafted and approved by the FDS and NIH. Clinical evaluation of the new pertussis toxoid vaccine in humans is now beginning.

百日咳的发病率已得到控制，通过使用我们目前的整体 细胞百日咳疫苗。 百日咳鉴定的新进展 毒素（PT）作为抗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。 目前的项目集中于开发生产方法 以及中和毒性作用和评估 对所得到的百日咳类毒素疫苗的免疫应答。 增长 已经开发了生产PT的条件和纯化方法 临床研究所需的数量。 用于监测的测定方法 实验疫苗的毒性和毒性中和 准备已经建立。 此外，方法已经 用于监测类毒素PT的残留抗原性 制备，并监测小鼠中对PT-类毒素的免疫应答， 猴和人类，并测量疫苗在小鼠和 组织培养 已经开发出了消除百日咳毒素的方法， 制备百日咳类毒素。 我们实验室制备的百日咳类毒素， 仅显示最低水平的残留毒性活性，而抗原性 活动仅部分减少。 实验疫苗制备 氢氧化铝吸附百日咳类毒素具有高度抗原性 并引发PT特异性免疫应答。 接种百日咳疫苗 类毒素保护小鼠抵抗细菌和毒素的攻击和刺激 血清抗体，在CHO细胞试验中中和PT。 免疫 幼年恒河猴接种疫苗后， PT中和抗体。 基于安全性和免疫原性 在动物中，疫苗的临床研究方案已经 由FDS和NIH起草并批准。 新的临床评价 人类百日咳类毒素疫苗已经开始使用。