Monoclonal Immunoprotectants for Select Agents Toxins (Mab-SAT)

描述（由申请人提供）：将广泛适用的抗体发现技术与快速，可扩展的制造平台相结合，将开发针对两种B类选择剂，产气荚膜梭菌（CP） epsilon毒素（ETX）和葡萄球菌肠毒素B （SEB）的人单克隆抗体（Mab）免疫保护剂。在一个共同的发现和制造平台上开发对抗这两种毒素的产品，其协同效应将体现为节省成本和时间。该项目将作为这些平台的概念验证，这些平台应可推广用于开发针对其他生物战剂以及新出现和再出现的传染病的人类单抗免疫保护剂。在特异性目标1中，我们将在体外评估一组人抗etx和抗seb单克隆抗体。最佳中和剂将在特异性靶2中对ETX和SEB中毒小鼠模型进行评估。针对每种毒素的三种最佳单克隆抗体将在Specific Aim 3的烟草酸制造系统中生产，针对ETX和SEB的主要单克隆抗体将根据体内活性、表达和稳定性数据进行选择。在Specific Aim 4中，所有ind启用活动都将以提交每个候选产品的ind为最终目标完成。这项工作的长期目标是抗etx和抗seb单克隆抗体的商业化。预期的免疫保护剂将是可注射的，用于预防和/或治疗人类。最终的商业化产品将是冻干制剂（在注射前立即重组），以最大限度地提高在各种环境条件下的稳定性。

DESCRIPTION (provided by applicant): Coupling a broadly applicable antibody discovery technology with a rapid, scalable manufacturing platform, human monoclonal antibody (Mab) immunoprotectants against two Category B Select Agents, Clostridium perfringens (CP) epsilon toxin (ETX) and staphylococcal enterotoxin B (SEB) will be developed. The synergistic effect of pursuing products against both toxins on a common discovery and manufacturing platform will manifest as savings in costs and time. This project will serve as a proof-of-concept for these platforms which should be generalizable for the development of human Mab immunoprotectants against other bio-warfare agents, as well as newly emerging and re-emerging infectious diseases. In Specific Aim 1, we will evaluate a panel of human anti-ETX and anti-SEB Mabs in vitro. The best neutralizers will be evaluated in Specific Aim 2 in mouse models of ETX and SEB intoxication. The three best Mabs against each toxin will be produced in a Nicotiana benthamiana manufacturing system in Specific Aim 3, and the lead Mab for ETX and SEB will be selected based on in vivo activity, expression, and stability data. In Specific Aim 4, all IND-enabling activities will be completed with a final goal of submitting INDs for each product candidate. The long-term objective of this effort is the commercialization of anti-ETX and anti-SEB Mabs. The envisioned immunoprotectants will be injectable, for prophylaxis and/or therapy in humans. The final commercialized product will be a lyophilized formulation (to be reconstituted immediately prior to injection) to maximize stability across a wide range of environmental conditions.