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) 使用专有方法生产了噬菌体展示 表达针对委内瑞拉马脑脊髓炎的人抗体片段 (Fab) 的文库 来自已免疫军事人员的病毒（VEEV）。这些抗体是用作 免疫疗法用于治疗有暴露于 VEEV 风险的个体，并评估人类 抗 VEEV 抗体库。中和抗体，通过动物疫苗接种或被动产生 对动物宿主施用，已被证明可以为动物提供针对 VEEV 的保护。通过一个 与 AAT 签订合同，两个 VEEV 中和 Fab 片段 P3F5 和 P3G1 将被转化为完整 IgG 用于表达、纯化和表征。表征还包括表位鉴定 作为人类抗体的体外和体内中和能力，将在 CDC 进行 实验室。然后，通过执行更多操作，将生成针对 VEEV 的更大的人类 Fab 小组 对现有噬菌体展示抗体库进行广泛筛选以及构建新的噬菌体展示库 来自其他军事人员的骨髓，具有针对 TC-83（VEEV 疫苗株）的血清滴度。 新分离的抗 VEEV Fab 将在 CDC 进行表征，以比较人类抗 VEEV 抗体 与 CDC 之前使用明确定义的鼠抗 VEEV 抗体库定义的库 鼠单克隆抗体组。