Research at Wichita State University has developed a novel compound that is potentially useful as both an antitoxin and vaccine, providing epitopes for the production of antibodies against Bacillus anthracis, but preventing key steps in pathogenesis (pore formation and translocation of lethal factor into cells). The novel compound was created by incorporating and labeling an unnatural amino acid analogue 2-fluorohistidine into protective antigen (2-F-His PA). Anthrax toxin is a member of the class of bacterial toxins termed A-B toxins. The A moiety is the enzymatic portion of the toxin that catalyzes toxic effects within a target cell – for anthrax, it is edema factor (EF) and lethal factor (LF). The B moiety binds to a cellular receptor, forms channels in membranes and facilitates translocation of A moiety into the cell – for anthrax, it is protective antigen (PA). The 2-F-His PA replaces the wild-type PA in the reaction and internalizes the existing lethal factor. It was shown that the 2-F-His PA can bind to the receptor with an affinity similar to the wild type protein, carry out heptamer formation, and bind lethal factor to form a toxic complex, but cannot form a pore or translocate lethal factor into the cell.
The major advantage of the 2-F-His PA as an antitoxin (therapeutic) is its ability to block interactions between the wild-type PA and the host cell receptor, preventing pore formation and translocation of lethal factor into the cell. Current anthrax vaccines can form pores at low pH values.
- Effective – Blocks interactions between the wild-type PA and the host receptor.
- Less evasive – Harmless to host cells even in the presence of lethal factor.
- Safer – Cannot carry out pore formation when bound to the host cell receptor to translocate lethal factor into host cells.
- Antitoxin – therapeutic in the event of anthrax exposure.
- Vaccine – in the future, the PA will be developed as a vaccine against anthrax.
- Available for license and pending-patent.
- Potential for ongoing collaboration with inventor, James G. Bann, and Wichita State University researchers.
- Patent Status: US 7,731,979 B2