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.
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.
|Van Slyke, Greta; Sully, Erin K; Bohorova, Natasha et al. (2016) Humanized Monoclonal Antibody That Passively Protects Mice against Systemic and Intranasal Ricin Toxin Challenge. Clin Vaccine Immunol 23:795-9|
|Sully, Erin K; Whaley, Kevin J; Bohorova, Natasha et al. (2014) Chimeric plantibody passively protects mice against aerosolized ricin challenge. Clin Vaccine Immunol 21:777-82|
|O'Hara, Joanne M; Yermakova, Anastasiya; Mantis, Nicholas J (2012) Immunity to ricin: fundamental insights into toxin-antibody interactions. Curr Top Microbiol Immunol 357:209-41|
|O'Hara, Joanne M; Whaley, Kevin; Pauly, Michael et al. (2012) Plant-based expression of a partially humanized neutralizing monoclonal IgG directed against an immunodominant epitope on the ricin toxin A subunit. Vaccine 30:1239-43|