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: 3919312
• 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/3919312
• 关键词: Bordetella pertussis; affinity chromatography; antibacterial antibody; antibody neutralization test; bacterial toxins; bactericidal immunity; biotechnology; communicable disease control; enzyme linked immunosorbent assay; human subject; human tissue; immunological substance; microorganism culture; pertussis; pertussis toxin; pertussis vaccine; preschool child (1-5); tissue /cell culture; toxoids

The incidence and severity of pertussis have been controlled by widespread immunization with DTP which contains inactivated Bordetella pertussis organisms (cellular vaccine). The identification of pertussis toxin, an extracellular protein of this pathogen, as a major, if not the sole protective antigen, was the basis for producing a new vaccine with improved safety and immunogenicity characteristics. B. pertussis was cultivated in a 100L fermenter and the pertussis toxin extracted from the culture supernant by affinity chromatography. The pertussis toxin was inactivated by hydrogen peroxide treatment under controlled conditions. The resultant toxoid, NICHD-PTxD, had less than 1% of its original binding and enzymatic activities by in vitro assays. In vivo assays, which require binding and enzymatic activity on the same molecule, showed no residual activity. Based upon the clinical satisfactory and serologic response in adults injected with this toxoid, two clinical studies with this pertussis toxoid have been completed in 18 month old children. The first, in Boston, gave one injection into 18 month old children previously immunized during infancy with the recommended three doses of DTP. The second gave two, and in some cases three injections, of this toxoid in Swedish children without previous history of either pertussis or known DTP vaccination. The results of both studies show that the pertussis toxoid has both superior safety and immunogenicity characteristics compared to the cellular vaccine component of DTP. The new batch of pertussis toxoid has been formulated and clinical testing of this material for safety immunogenicity in infants and, hopefully, effectiveness in that age group is planned.

百日咳的发病率和严重程度已得到控制， 用DTP广泛免疫， 百日咳博德特氏菌（细胞疫苗）。 的 百日咳毒素一种胞外蛋白鉴定 病原体，作为一个主要的，如果不是唯一的保护性抗原，是 生产安全性提高的新疫苗的基础， 免疫原性特征 B。百日咳是在一个 100 L发酵罐和从培养物中提取的百日咳毒素 通过亲和层析将上清液纯化。 百日咳毒素是 在受控条件下用过氧化氢处理灭活 条件 得到的类毒素NICHD-PTxD具有小于1%的 通过体外测定其原始结合和酶活性。 体内测定，其需要对所述蛋白质的结合和酶活性。 相同的分子，没有显示出残留活性。 基于 成人注射后的临床满意度和血清学反应 有两个关于百日咳类毒素的临床研究 已在18个月大的儿童中完成。 第一次发生在 波士顿，以前给18个月大的孩子注射过一次 在婴儿期接种推荐的三剂DTP。 第二组注射了两次，有时是三次， 瑞典儿童中的类毒素， 百日咳或已知的百白破疫苗接种。 两项研究的结果 表明百日咳类毒素具有上级安全性， 与细胞疫苗相比的免疫原性特征 DTP的组成部分。 新一批百日咳类毒素已经 该材料的安全性配制和临床试验 在婴儿中免疫原性，并希望在老年人中有效 集团计划。