Application Protocols for a DNA Vaccine Against Anthrax

描述（由申请人提供）：炭疽，一种由炭疽芽孢杆菌引起的传染病，由于其潜在的生物战用途而成为一个紧迫的问题，最有可能通过雾化炭疽孢子传播，导致致命的吸入性炭疽。目前的疫苗通过诱导针对炭疽毒素的抗体来提供保护，但存在显著缺陷，包括可用性有限、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。一种针对炭疽毒素的DNA疫苗将是经济的，相对容易制备、储存和标准化，应该会产生很少的副作用，如果有的话。它还允许包含几种明确定义的抗原。DNA疫苗的应用方法对其效力至关重要。疫苗将通过电穿孔递送，因为这种方法提供一致、高水平、可扩展的免疫原表达，这与高强度、持久的抗体反应相关。给药方案将在大鼠中精确定义。协议将使用专有的缩放算法在兔子身上进行缩放。读数将包括毒素中和抗体滴度，这被认为是免疫的相关。方案诱导高强度，功能性免疫将在兔子身上进行测试，以防止吸入攻击。

DESCRIPTION (provided by applicant): Anthrax, an infectious disease caused by Bacillus anthracis, became a pressing concern because of its potential biowarfare use, most likely via aerosolized anthrax spore dissemination, resulting in deadly inhalation anthrax. The current vaccine, which confers protection by inducing antibodies against anthrax toxin, 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 directed against anthrax toxin would be economical, relatively easy to prepare, store and standardize, should induce few, if any, side effects. It would also permit the inclusion of several clearly defined antigens. The method of application of a DNA vaccine is critical for efficacy. Vaccine will be delivered by electroporation because this method provides consistent, high level, scalable immunogen expression, which correlates with high magnitude, durable antibody responses. Dosing protocols will be precisely defined in rats. Protocols will be scaled-up in rabbits using a proprietary scaling algorithm. Readouts will include toxin-neutralizing antibody titers, which are considered a correlate for immunity. Protocols inducing high-magnitude, functional immunity will be tested in rabbit for protection against inhalation challenge.