Potentiating an anthrax DNA vaccine with electroporation

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Anthrax suddenly became a pressing public health issue due to the present terrorist crisis. Its use as biological weapon causes death by inhalational anthrax, due to exotoxins produced by anthrax bacteria. The current vaccine has significant drawbacks including limited availability, lack of standardization and quality control, the need for repeated injections, and frequent occurrence of side effects, making it inadequate for use in large populations. A new vaccine is urgently needed. A DNA vaccine would be economical, relatively easy to prepare, store and standardize, should induce few, if any, side effects, and would permit the inclusion of several clearly defined antigens. Electroporation is a promising method for DNA vaccine delivery because of its ability to provide consistent, high level, scalable immunogen expression, which correlates with high magnitude antibody responses. Antibody response against anthrax toxin is a correlate for immunity. Antibody titers following electroporation mediated DNA vaccination will be measured in time course and dose response experiments. Toxin neutralizing antibodies will be assessed. Procedures will be tested and optimized in mice. Initial scale-up testing will be done in rats. Protocols matching predefined criteria will be tested in Phase II in larger animals and in experimental models of inhalational anthrax.