Monoclonal antibodies for anthrax prophylaxis and diagnosis.
Thomas Kozel

There are four distinct stages in the evolution of an anthrax infection. First, there is an immediate-early ingestion of spores by macrophages followed by intracellular germination of endospores. Second, there is outgrowth of the bacillus within the macrophage environment and escape. Third, there is massive extracellular growth of the bacterium with a consequent production of the anthrax toxin and other virulence factors. Finally, the toxin acts on cellular targets leading to host symptoms and death. Studies by Dr. Thomas Kozel are aimed at the production of monoclonal antibodies that are reactive with the poly-D-glutamic acid capsule of Bacillus anthracis. Production of disease and release of toxin requires extracellular survival and growth of the bacterium. Opsonic anticapsular antibodies have the potential to facilitate clearance of the bacterium before a sufficient amount of toxin is released to lead to host symptoms and death. Prophylactic use of anticapsular antibodies for exposed individuals has particular value because this approach to prevention would not be influenced by genetic manipulation of the bacterium to produce antibiotic resistance or a toxin that is resistant to current or proposed toxoid based vaccines. Anticapsular monoclonal antibodies also have considerable potential for use in diagnosis of individuals with suspected anthrax. Although extracellular release of capsular material during systemic infection has not been studied experimentally, it is highly likely that the capsular material is shed into serum, possibly in large amounts. If this is the case, an antibody based diagnostic tool could greatly reduce the time needed to establish a diagnosis.