Potentiating an anthrax DNA vaccine with electroporation

描述（由申请人提供）：由于目前的恐怖主义危机，炭疽突然成为一个紧迫的公共卫生问题。由于炭疽细菌产生的外毒素，使用炭疽作为生物武器会导致吸入性炭疽死亡。目前的疫苗存在重大缺陷，包括可得性有限、缺乏标准化和质量控制、需要反复注射以及经常发生副作用，因此不适合在大量人群中使用。迫切需要一种新的疫苗。DNA疫苗将是经济的，相对容易制备、储存和标准化，应该产生很少的副作用，如果有的话，并且允许包含几种明确定义的抗原。电穿孔是一种很有前途的DNA疫苗递送方法，因为它能够提供一致的、高水平的、可扩展的免疫原表达，这与高强度的抗体反应相关。针对炭疽毒素的抗体反应与免疫有关。电穿孔介导的DNA疫苗接种后的抗体滴度将在时间过程和剂量反应实验中测定。将评估毒素中和抗体。程序将在小鼠中进行测试和优化。最初的扩大试验将在大鼠身上进行。符合预定标准的方案将在第二阶段在较大动物和吸入性炭疽实验模型中进行测试。

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.