Immunotherapy for Pulmonary Anthrax

DESCRIPTION (provided by applicant): Our overall goal in this project is to make available in large quantity an inexpensive recombinant protein that protects against the cellular toxicity associated with inhalational (pulmonary) anthrax. We will combine our experience in producing functional antibodies and immunoconjugates in transgenic plants with the Anthrax Toxin Receptor (ATR), and with high-affinity antibodies against the anthrax exotoxins.. Spores of Bacillus anthracis, the causal agent of anthrax are a major biological threat agent that may be used by bioterrorists to threaten troops in the battlefield or civilians here at home. An anthrax vaccine has been developed, but protective immunity takes months to develop and is, at present, available only to members of the military. Antibiotic therapy can be successful only if initiated before symptoms appear. Because it is possible to be exposed to anthrax without knowing it, it is desirable to develop a treatment that could be effective even after symptoms appear. It has been shown that a recombinant soluble form of the cellular receptor to which the anthrax toxin binds could block the action of the toxin in vitro. We propose to genetically fuse the anthrax toxin receptor to an IgG1 heavy chain constant region, creating a chimeric molecule called an "immunoadhesin", which could be much more effective than the soluble receptor alone. Additionally, we propose to express in plants a recently developed high-affinity antibody to the anthrax toxin. At present, plants offer the best system for the large scale, inexpensive production of this kind of recombinant protein. In the first phase of this research, we will use a plant-based transient expression system to produce small quantities of two different recombinant proteins and test them for neutralization activity against anthax toxins. In a second phase, the most effective construct would be used to generate stably transformed plants that could be grown on an agricultural scale. We estimate that plants will facilitate the production of metric ton quantities of an anthrax-protective protein at 1-5% of the cost of steel tank bioreactors. Plantibody technology will greatly reduce the costs to stockpile these proteins for protection of the entire US population from this serious threat.