PASSIVE IMMUNIZATION--TREATING RABIES WITH HUMAN MAB

被动免疫——用人单克隆抗体治疗狂犬病

• 批准号: 2306927
• 负责人: HILARY KOPROWSKI
• 金额: $ 33.38万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-10 至 1997-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2306927
• 关键词: PASSIVE; IMMUNIZATION; TREATING; RABIES; HUMAN

The objective of this project is to generate rabies virus neutralizing human monoclonal antibody (mAbs), preferentially of the high affinity IgG isotype, so that a "cocktail" of several neutralizing human mAbs can be prepared against multiple antigenic sites on the viral glycoprotein (GP) and ribonucleoprotein (RNP) complex. Specifically, this project aims to: (l) generate at least 15 high-affinity, virus-neutralizing human mAbs against various antigenic determinants on rabies virus using human hybridoma technology and (2) show that these mAbs protect animals against lethal rabies challenge. B cells isolated from peripheral blood (10-14 days) after booster vaccine) will be immortalized by infection with EBV, and cells producing rabies virus-specific antibody, detected in culture supernatants by ELISA, will be fused to produce mouse-human hybrids. These hybrids will be cloned, and cells producing rabies virus-specific antibody expanded. Rabies virus-specific mAbs generated in this fashion will be fully characterized in vitro for isotype, specificity, affinity, and VNA titre and in vivo for post-exposure efficacy in mice and the Syrian hamster model.

该项目的目的是产生狂犬病病毒中和