Human Monoclonal Antibodies for VEE Virus

使用专有方法Alexion抗体技术(AAT)，已经产生了噬菌体展示 针对委内瑞拉马脑脊髓炎的人抗体片段(Fab)表达文库 来自接种疫苗的军事人员的病毒(VEEV)。这些抗体是用作 免疫疗法在治疗暴露于VEEV风险人群中的作用 抗VEEV抗体谱系。中和抗体，通过在动物中接种疫苗或被动地产生 给动物宿主使用，已被证明为动物提供了对VEEV的保护。通过一个 与AAT签订合同，VEEV的两个中和抗体P3F5和P3G1将转换为全免疫球蛋白 用于表达、纯化和鉴定。表征还将包括表位鉴定。 作为人抗体的体外和体内中和能力，将在疾病预防控制中心进行 实验室。然后，通过执行更多针对VEEV的人类Fabs将生成更大的面板 广泛筛选现有的噬菌体展示抗体库，以及构建新的噬菌体展示库 从更多具有TC-83(VEEV疫苗毒株)血清效价的军事人员的骨髓中提取。 新分离的抗VEEV抗体将在疾控中心进行鉴定，以比较人抗VEEV抗体 疾病预防控制中心先前使用明确定义的 一组鼠源性单抗。

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.