Immunization with transition state analogues to detoxify chemical weapons
Abstract
In order to protect warfighters against chemical weapons, we propose to develop a strategy for immunizing with transition state analogues (TSAs) that will raise catalytic antibodies against the chemical weapons, allowing detoxification by the immune system. In essence, we are suggesting that human versions of bacterial organophosphate hydrolases (OPHs) that have been considered for detoxification and decontamination could be generated in a living system. We will proof this strategy in mice, as a prelude to attempting to develop systemic, long-term immunities against chemical weapons in military personnel. Back-of-the-envelope calculations suggest that even a modest increase in catalytic activity in an immunized organism can have a major impact on toxicity. Even if this approach is only partially successful it will have a huge impact on preparedness, as it may substantively increase the time to administration of conventional antidotes, such as atropine. In line with this consideration, we for the first time propose a novel strategy in which the immune system is augmented on demand with cofactors (oximates) that can fit into the combining sites of antibodies, greatly improving their catalytic potential for the hydrolysis of sarin and soman.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- HDTRA11810030
Entities
People
- Andrew D Ellington
Organizations
- Defense Threat Reduction Agency
- University of Texas at Austin