Ricin Toxin Protective Monoclonal Antibodies with Improved Serum Half-Life

Ricin is a category B toxin due to its ease of acquisition, dissemination, and the high potential for morbidity and mortality after exposure. Ricin in semi-purified or purified form is extremely toxic to humans following injection, inhalation, or ingestion and has been used as an agent of bioterrorism. Ricin was recently detected in U.S. government facilities. There are currently no methods of preventing or treating ricin exposurethis represents a major unmet need for protection of civilians and warfighters. Passive immunization with monoclonal antibodies (mAbs) has been shown to be effective against a wide variety of infectious agents and toxins. We have identified a highly potent anti-ricin mAb, mPB10. This mAb was shown to protect mice when administered prior to and after ricin challenge. The purpose of this Phase 2 proposal is to prolong the effectiveness of the PB10 mAb to six months after a single injection. This will be accomplished by introducing mutations into the PB10 sequence that are known to increase serum half-life by five-fold. Evaluation of the mAb half-life will be in non-human primates (NHPs). A challenge study where NHPs are administered the PB10 mAb prior to exposure to aerosolized ricin will be conducted.