Development of a monoclonal immunoprotectant for ricin

描述（由申请人提供）：美国国立卫生研究院已将开发针对潜在生物恐怖主义制剂的治疗方法视为国家研究重点。对蓖麻毒素的解毒剂有特别的需求（NIAID，2004年）;疾病控制中心估计，500微克蓖麻毒素是人体通过注射或吸入接触的致死剂量。蓖麻毒素是一种B类特选制剂，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制剂（Maman和Yehezkelli，2005年; Stone，2002年）。这种毒素已被用于暗杀，最近在一些政府设施中发现，包括南卡罗来纳州的邮政设施和递送到美国参议院办公室的信封中（Hulse，2004;希耶等人，2007年）。由于蓖麻毒素的毒性和易于从蓖麻子（蓖麻子）中制备，公共卫生官员和国防机构共同努力制定保护平民和军事人口的对策。目前还没有预防或治疗蓖麻毒素中毒的药物。已证明用抗体进行被动免疫可有效对抗多种毒素（Casadevall，2002）。由于其优异的安全性和有效性，单克隆抗体（mAb）是一类快速增长的治疗药物。一种高度有效的鼠抗蓖麻毒素mAb，GD 12（Neal等人，2009）已经被研究者之一（Dr. Mantis）鉴定，并且显示当在全身或粘膜蓖麻毒素攻击之前施用时保护小鼠。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克隆抗体产品。设想的注射产品将在蓖麻毒素暴露之前和/或之后用于人类。 公共卫生相关性：该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战剂，目前还没有治疗方法。

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.