Human Monoclonal Antibodies for VEE Virus

VEE 病毒人单克隆抗体

• 批准号: 7641030
• 负责人: CAROL D BLAIR
• 金额: $ 25.51万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7641030
• 关键词: Animals; Antibodies; Antibody Repertoire; Bone Marrow; Centers for Disease Control and Prevention (U.S.); Contracts; Epitopes; Exposure to; Human; Immunoglobulin Fragments; Immunoglobulin G; Immunotherapeutic agent; In Vitro; Individual; Laboratories; Libraries; Methodology; Military Personnel; Monoclonal Antibodies; Mus; Pan Genus; Phage Display; Risk; Screening procedure; Serum; Technology; Vaccination; Vaccines; Venezuelan Equine Encephalitis Virus; human monoclonal antibodies; in vivo; neutralizing antibody

Using proprietary methodologies, Alexion Antibody Technologies (AAT), has produced phage display libraries expressing human antibody fragments (Fab) directed against Venezuelan equine encephalomyelitis virus (VEEV) from immunized military personnel. These antibodies are strong candidates for use as immunotherapeutics in the treatment of individuals at-risk of exposure to VEEV, and to assess the human anti-VEEV antibody repertoire. Neutralizing antibodies, either raised by vaccination in animals or passively administered to animal hosts, have been shown to provide protection in animals against VEEV. Through a contract with AAT, two VEEV neutralizing Fab fagments, P3F5 and P3G1, will be converted into whole IgG for expression, purification, and characterization. Characterization will include epitope identification, as well as the in vitro and in vivo neutralizing capacity of the human Abs and will be performed in the CDC laboratory. A larger panel of human Fabs directed against VEEV will then be generated by performing more extensive screens of existing phage display antibody libraries as well as building a new phage display library from the bone marrow of additional military personnel with serum titer against TC-83 (VEEV vaccine strain). Newly isolated anti-VEEV Fabs will be characterized at CDC to compare the human anti-VEEV antibodiy repertoire to the murine anti-VEEV antibody repertoire as defined previously by the CDC using a well-defined panel of murine monoclonal antibodies.

Alexion Antibody Technologies（AAT）使用专有方法， 表达针对委内瑞拉马脑脊髓炎的人抗体片段（Fab）的文库 病毒（VEEV）免疫的军事人员。这些抗体是用于作为 在治疗有暴露于VEEV风险的个体中使用免疫治疗剂，并评估人类 抗VEEV抗体库。中和抗体，通过动物接种疫苗或被动接种疫苗产生 已显示向动物宿主施用的抗VEEV药物在动物中提供针对VEEV的保护。通过 通过与AAT的合同，将两个VEEV中和Fab片段P3 F5和P3 G1转化为完整的IgG 用于表达、纯化和表征。表征还将包括表位鉴定 作为人Ab的体外和体内中和能力，并将在CDC进行 实验室然后将通过进行更多的实验来产生更大的针对VEEV的人Fab组。 广泛筛选现有噬菌体展示抗体库以及构建新的噬菌体展示库 来自具有抗TC-83（VEEV疫苗株）血清滴度的其他军事人员的骨髓。 新分离的抗VEEV Fab将在CDC进行表征，以比较人抗VEEV抗体 使用定义明确的抗体库，将鼠抗VEEV抗体库与CDC先前定义的鼠抗VEEV抗体库进行比较。 一组鼠单克隆抗体。