New Generation of Anthrax Prophylaxis and Therapy

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DESCRIPTION (provided by applicant): This Phase I SBIR application addresses the NIAID call for high priority biodefense products such as novel vaccines and therapeutics to protect our nation against various biothreat agents. Although these types of proposals do not require a significant amount of preliminary data, we have already performed substantial preliminary experimental work that encourages us to pursue an innovative and revolutionary approach for developing anti-anthrax preventive and therapeutic preparations. Within a short 12-month study, we plan to prove its effectiveness by developing novel multivalent anti-anthrax antibodies and multivalent anthrax peptide vaccine. These preparations will be based on the use of antigens identified in the active centers of extracellular and membrane-bound metalloproteinases of Bacillus anthracis. We decided to use these targets for the following reasons: a) Bacterial proteinases are recognized as virulence factors in a number of infectious diseases b) Recent discoveries have made it possible to identify sequence motifs of metalloproteinases. Consequently, it is now possible to identify specific amino acid sequences of "virulent" metalloproteinases for use as peptide vaccine candidates and as peptide molecules for immunization to generate both polyclonal and monoclonal antibodies for the prophylaxis and treatment of anthrax c) It has been proven that short peptides are immunogenic, can be easily manufactured, may be used for production of highly pure vaccines and can be combined as "cocktails" of peptides for the development and manufacture of multivalent/multiepitope and multiagent vaccines and antibodies. We have already finished our "proof-of principle" study and propose to develop a new anthrax vaccine and anti-anthrax antibodies with the following specific aims: 1). Synthesis, purification and conjugation of peptide antigens as candidates for multivalent vaccine and antibody development; 2). Immunization of mice with the peptide vaccine candidates and testing of specific anti-anthrax immunity generated by a single peptide candidate and a combination thereof; 3). Generation of specific anti-anthrax antibodies against the selected peptides and testing their protective efficacy in the murine model.