Development of a monoclonal immunoprotectant for ricin

描述(由申请者提供)：美国国立卫生研究院已将针对潜在生物恐怖主义毒剂的治疗药物的开发视为国家研究重点。特别需要针对蓖麻毒素的解毒剂(NIAID，2004年)；疾病控制中心估计，通过注射或吸入接触到的人中，500微克的蓖麻毒素是致命剂量。蓖麻毒素是一种B类选择毒剂，在第二次世界大战期间被美国和其他国家武器化，并被用作生物恐怖主义的毒剂(Maman和Yehezkelli，2005；Stone，2002)。这种毒素曾被用于暗杀，最近在一些政府设施中发现了这种毒素，包括南卡罗来纳州的一家邮政设施和寄往美国参议院办公室的信封(Hulse，2004；Schier等人，2007)。由于蓖麻毒素的毒性和易于从蓖麻豆中提取，世界卫生组织已与公共卫生官员和国防机构共同努力，制定保护平民和军人人口的对策。目前还没有预防或治疗蓖麻毒素中毒的药物。用抗体进行被动免疫已被证明对多种毒素有效(Casadevall，2002)。由于其良好的安全性和有效性，单抗(MAbs)是一类迅速增长的治疗药物。一种高效的小鼠抗蓖麻毒素单抗GD12(Neal等人，2009年)已经被一名研究人员(Mantis博士)发现，并被证明在全身或粘膜蓖麻毒素攻击之前给药对小鼠具有保护作用。本项目的长期目标是开发一种安全有效的蓖麻毒素中毒单抗产品。设想的可注射产品将在人类接触蓖麻毒素之前和/或之后使用。 与公共卫生相关：本提案中的努力将有助于开发一种药物，用于预防和/或治疗蓖麻毒素中毒，蓖麻毒素是一种潜在的生物制剂，目前尚无治疗方法。

DESCRIPTION (provided by applicant): The National Institutes of Health has deemed the development of therapeutics against potential bioterrorism agents as a national research priority. There is a particular need for antidotes against the toxin ricin (NIAID, 2004); the Centers for Disease Control estimates that 500 micrograms of ricin is a lethal dose in humans exposed via injection or inhalation. Ricin, a Category B Select Agent, was weaponized by the U.S. and other countries during World War II and has been used as an agent of bioterrorism (Maman and Yehezkelli, 2005; Stone, 2002). This toxin has been used in assassinations, and it was recently uncovered in a number of government facilities, including a South Carolina postal facility and in envelopes delivered to offices of the U.S. Senate (Hulse, 2004; Schier et al., 2007). Because of ricin's toxicity and ease of preparation from the castor bean (Ricinus communis), have mounted a concerted effort by public health officials and defense agencies to develop countermeasures for protecting civilian and military populations. There are currently no drugs available for preventing or treating intoxication with ricin. Passive immunization with antibodies has been shown to be effective against a wide variety of toxins (Casadevall, 2002). Because of their excellent safety profile and efficacy, monoclonal antibodies (mAbs), are a rapidly growing class of therapeutic drugs. A highly potent murine anti-ricin mAb, GD12, (Neal et al., 2009) has been identified by one of the investigators (Dr. Mantis) and shown to protect mice when administered prior to systemic or mucosal ricin challenge. The Long Range Objective of this project is to develop a safe and effective mAb product for ricin intoxication. The envisioned injectable product will be for use in humans prior to and/or after ricin exposure. PUBLIC HEALTH RELEVANCE: The efforts in this proposal will help in the development of a drug for preventing and/or treating intoxication with ricin, a potential biowarfare agent, for which no treatment currently exists.