Anthrax was developed as a biowarfare agent by the US government and a number of other countries. Despite treaties and resolutions to terminate these programs, anthrax remains a very real, world defense issue. Since an anthrax vaccine will be a critical component of any effective defense plan, our objective is to find one. Vaccine efforts for anthrax have focused almost entirely on improving the purification or formulation of PA or one of the other toxin antigens. We believe that vaccine components that target the spore or bacterium directly will be important in protecting both military and civilian populations against both natural and especially bio-engineered anthrax disease. Therefore, we propose to screen all the genes of Bacillus anthracis for their ability to protect against inhalation anthrax in mice. Our approach will be to build all anthrax ORFs as gene vaccines, and then design a matrix arraying system that allows us to screen the high complexity library down to a few vaccine candidates in one animal challenge experiment. The underlying functional genomic methods were developed with DARPA funding: expression library immunization and linear expression elements. These platform technologies make our approach technically feasible, and their utility has been validated in our labs. We are now poised for their application to anthrax. Specifically, our aims will be to generate the more than 4,000 genes of B. anthracis as more than 14,000 overlapping gene fragments that are capable of uniformly high-level expression. Using our unique technologies, vaccine candidates will be identified quickly. Immune assays will be used to direct the optimization of protection in rodents. Then, a set of our best candidates will be tested in rabbits against an inhalation anthrax challenge. At the completion of this project, we will deliver a set of broad-based vaccine candidates against anthrax that might be administered with or without toxin antigens. These will be ready for preclinical trials. We should also have in place a high-throughput antigen discovery system that could be applied to other biothreat and emerging pathogens.
