The overall objective of this phase I SBIR proposal is to develop therapeutic antibodies for passive immunotherapy in acute anthrax, including the highly lethal inhalational form of anthrax. We will use codon-optimized plasmid DNAs (DNA vaccines) to immunize experimental animals to produce anti-anthrax antibodies suitable for human use in passive immunization. This would enable an immunization strategy that would supplement antibiotic therapy regimens to improve the survival of patients with anthrax. The antibodies prepared will be high titer, specific polyclonal antibodies to Bacillus anthracis protective antigen (PA) that can neutralize PA and block formation of anthrax toxin complexes. As part of these studies we will purify IgG from hyperimmune serum and determine the levels of neutralizing activity obtained. Because of the high failure rate of antibiotic therapy there is a clear need for development of a strategy for passive immunization against anthrax. In our preliminary studies, we at Antibody Sciences, Inc. have obtained toxin-neutralizing antibody by DNA immunization equivalent to the protective titers obtained by others in animals that received active immunization with an anthrax vaccine. Our techniques for DNA immunization permit quick production of high titer antisera without the need for purification of B. anthracis antigens from bacterial cultures or from cell-culture expressed antigens. DNA immunization offers a highly standardized and low cost process to produce large quantity of antibodies. Therefore, the high titer antibody we can produce will enable stockpiling of sufficient quantities of antibody for immunotherapy should attacks with B. anthracis occur. At the end of this phase 1 study, a standardized schedule will be established in phase II to prepare for large-scale production and testing of this much needed, perhaps essential, product in biodefense against anthrax attacks
