Human Abs to B. Anthracis in Cloned Transgenic Cattle

DESCRIPTION (provided by the applicant): Anthrax is considered a possible bioterrorist threat because of its lethality and its durability. Several nations have had bioweapons programs in the past that produced large quantities of anthrax. Numerous anthrax scares and the recent deaths from exposure to anthrax spores sent through the mail have heightened concerns about protecting the population against anthrax. No mass vaccination program is envisioned because the existing anthrax vaccine is in short supply. In the absence of a vaccine, passive immunization with intravenous immunoglobulin (IVIG) of people exposed to anthrax spores is a reasonable strategy. This proposal is to develop a large animal system for producing human polyclonal antibody against anthrax. It has been shown that transgenic mice carrying an artificial human chromosome (HAC) produce human antibody of all classes and with a broad repertoire when challenged with antigen. In the current work, a similar strategy would be applied to cattle, where the yield of antibody would be far greater than with mice. We have already shown that we can create cattle clones that have a HAC containing the human IG genes, and that the chromosome is stable and is expressed throughout fetal development into neonatal life. Work is proposed to characterize the immune response to anthrax vaccine and purified anthrax proteins in normal and in cloned calves. This novel and practical solution to the limited supply of human IVIG has several advantages. First, it would enable the production of large quanitites of human antibody at a reasonable cost. Second, it would provide greater flexibility in designing immunization strategies for producing high, titer, high specificity antibody beyond what is possible with human volunteers. Third, it would provide a new enabling technology for producing clinically important human antibody reagents against other bacterial and viral pathogens.