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)表型毒素(ETX)和葡萄球菌肠毒素B(SEB)的人源单抗(Mab)免疫保护剂。在一个共同的发现和制造平台上开发针对这两种毒素的产品的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，应可推广到开发针对其他生物战剂以及新出现和重新出现的传染病的人类单抗免疫保护剂。在具体目标1中，我们将对一组人源性抗ETX和抗SEB单抗进行体外评价。最好的中和剂将在ETX和SEB中毒的小鼠模型中进行特定目标2的评估。针对每种毒素的三个最好的单抗将在特定目的3的本氏烟草制造系统中生产，并将根据体内活性、表达和稳定性数据选择ETX和SEB的前导单抗。在具体目标4中，将完成所有支持IND的活动，最终目标是为每个候选产品提交IND。这一努力的长期目标是将抗ETX和抗SEB单抗商业化。设想的免疫保护剂将是可注射的，用于人类的预防和/或治疗。最终的商品化产品将是冻干制剂(在注射前立即重新配制)，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.