Human Antibodies for Exposure/Protection from Anthrax

用于暴露/预防炭疽的人类抗体

• 批准号: 6853598
• 负责人: Wolfgang W Scholz
• 金额: $ 35.03万
• 依托单位: AVANIR PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6853598
• 关键词: Bacillus anthracis; SCID mouse; anthrax; anthrax toxin; antibacterial antibody; biotechnology; bioterrorism /chemical warfare; clinical research; combination chemotherapy; disease /disorder model; drug interactions; exotoxins; human subject; immunologic substance development /preparation; laboratory rat; microorganism disease chemotherapy; monoclonal antibody; neutralizing antibody; nonhuman therapy evaluation; passive immunization; protein binding; recombinant proteins

DESCRIPTION (provided by applicant): Avanir Pharmaceuticals Inc., has developed a powerful platform for the rapid generation of high affinity fully human monoclonal antibodies that can be selected on their ability to neutralize anthrax toxin PA as exemplified by our lead candidate 8C1 (Kd 1.2 x10-12M, KinExA). Here we propose to continue the development of 8C1 as well as to isolate and characterize additional totally human monoclonal antibodies (MAbs) against B. anthracis exotoxin components protective antigen (PA) and lethal factor (LF). We will evaluate and characterize Mabs for affinity (using BiaCore and KinExA) and toxin neutralization (using an in vitro cell-based assay). Selected candidates will be further evaluated in a rodent animal model, using bolus challenge with recombinant anthrax toxins. By using multiple human donors, we will access a diverse a panel of antibodies and determine the optimal candidate(s) or combination of antibodies required to neutralize anthrax exotoxin in vivo. At the completion of this proposed study we will have candidates ready to enter the next stage of animal model evaluation. Testing candidates in live animal models with exposure to aerosolized anthrax spores are beyond the scope/budget of this study and would be the logical entry point for a phase II application. The following Specific Aims will be performed: -1: Generate a panel of high affinity fully human antibodies to PA and LF components of the tripartite B. anthracis exotoxin. -2: Evaluate and characterize MAbs binding and efficacy in an in vitro protection assay. -3: Determine protective efficacy in a rodent animal model, using bolus challenge with recombinant anthrax toxins.

描述（由申请人提供）：Avanir制药公司开发了一个强大的平台，用于快速生成高亲和力的全人单克隆抗体，可以根据其中和炭疽毒素PA的能力进行选择，例如我们的主要候选物8C1 （Kd 1.2 x10-12M, KinExA）。在这里，我们建议继续开发8C1，并分离和鉴定更多的针对炭疽芽孢杆菌外毒素成分保护抗原（PA）和致死因子（LF）的全人源单克隆抗体（mab）。

项目成果

Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed.

• DOI: 10.1186/1476-8518-2-5
• 发表时间: 2004-05-12
• 期刊: Journal of immune based therapies and vaccines
• 作者: Sawada-Hirai, Ritsuko;Jiang, Ivy;Kang, Angray S
• 通讯作者: Kang, Angray S

Human monoclonal antibodies that neutralize anthrax toxin by inhibiting heptamer assembly.

通过抑制七聚体组装来中和炭疽毒素的人单克隆抗体。

• 发表时间: 2004
• 期刊: Human antibodies
• 作者: Wang,Fei;Ruther,Paul;Jiang,Ivy;Sawada-Hirai,Ritsuko;Sun,ShuMan;Nedellec,Rebecca;Morrow,PhillipR;Kang,AngrayS
• 通讯作者: Kang,AngrayS