HUMAN-MURINE CHIMERIC ABS VS RESPIRATORY SYNCYTIAL VIRUS

人-鼠嵌合 ABS 与呼吸道合胞病毒

• 批准号: 3489292
• 负责人: L Syd Johnson
• 金额: $ 5万
• 依托单位: MEDIMMUNE, INC.
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3489292
• 关键词: antiviral antibody; computer simulation; genetic manipulation; hybrid antibody; immunoglobulin genes; molecular dynamics; monoclonal antibody; neutralizing antibody; nucleic acid sequence; oligonucleotides; passive immunization; respiratory syncytial virus; technology /technique development; virus antigen

DESCRIPTION: (Adapted from the applicant's abstract) RSV is responsible for yearly epidemics of bronchiolitis and pneumonia in infants and young children. At risk of serious RSV morbidity are children with underlying disease, bronchopulmonary dysplasia and other pulmonary diseases, various congenital or acquired immunodeficiency syndromes and prematurity. A vaccine for immunization to prevent RSV infections is urgently needed. Unfortunately, RSV vaccines are unlikely to be licensed in the near future. The initial formalin inactivated RSV vaccine caused an increased incidence of RSV lower respiratory tract disease and death in immunized children. Therefore, the most promising approach to prophylaxis of RSV disease in high risk infants is passive immunization. Currently, intravenous hyperimmune globulin prepared from plasma containing high levels of anti-RSV antibody is being tested in high risk children for protective efficacy. However, a more reliable source of a highly defined and standardized product would be desirable. Murine MAbs against the F glycoprotein of RSV have been developed and characterized. These have been shown to neutralize RSV in vitro and protect cotton rats from lower respiratory tract infection in vivo. Previous studies with other rodent antibodies suggest that the development of human anti-mouse antibody responses would preclude the use of these murine antibodies directly in children. Therefore, it is the objective of this Phase I study to develop humanized derivatives of these anti-RSV antibodies which could then be developed as agents for passive immunization against RSV infection.

描述：（改编自申请人摘要）RSV负责 每年流行的细支气管炎和肺炎的婴儿和年轻人 孩子 存在严重RSV发病风险的儿童有基础疾病， 疾病、支气管肺发育不良和其他肺部疾病， 先天性或获得性免疫缺陷综合征和早产。 一 迫切需要用于免疫以预防RSV感染的疫苗。 不幸的是，RSV疫苗不太可能在近期获得许可。 未来 最初的福尔马林灭活RSV疫苗引起了 接种疫苗儿童RSV下呼吸道疾病发病率和死亡率 孩子 因此，最有希望的预防RSV的方法是 对高危婴儿进行被动免疫。 目前， 一种由高含量血浆制备的静脉注射用超免疫球蛋白 在高危儿童中检测抗RSV抗体水平， 保护功效 然而，一个更可靠的高度定义的来源， 并且标准化的产品将是期望的。 已经开发了针对RSV的F糖蛋白的鼠单克隆抗体， 表征了 这些已显示在体外中和RSV， 保护棉鼠体内下呼吸道感染。 先前对其他啮齿类动物抗体的研究表明， 人抗小鼠抗体反应的存在将妨碍这些抗体的使用 小鼠抗体直接用于儿童。 因此，它的目标是 这项I期研究旨在开发这些抗RSV的人源化衍生物， 然后可以开发抗体作为被动免疫的试剂， 针对RSV感染的免疫。