Prophylactic Anthrax Toxin Vaccine

描述（由申请人提供）：该STTR资助提案用于开发安全有效的炭疽毒素疫苗。目前世界范围内的威胁，使用炭疽孢子作为生物恐怖主义武器在军事战区以及对一般人口的关注，需要一个更有效的疫苗，以防止炭疽。在过去的几个月里，人们认识到，医学界很少有人看到人类感染炭疽，因此只有极少数人具备诊断和治疗炭疽的能力。安全有效的预防性疫苗将有效地消除这种形式的生物恐怖主义威胁。Price等人， 已经表明，由编码脱毒保护性抗原（PA）和致死因子（LF）的质粒DNA组成的疫苗保护小鼠免受使用5X致死剂量的毒性蛋白的静脉内攻击。基于这项工作和随后的工作（在这里介绍）表明，类似的DNA疫苗接种协议可以保护兔子免受更严格的孢子吸入挑战，这项拨款提出了支持在人类临床试验中测试DNA疫苗所需的临床前工作。这项工作将通过一系列实验方案推进FDA批准的编码PA或LF质粒的质粒DNA载体或PA + LF质粒组合的制剂，以证明在小鼠和兔中产生保护性免疫应答。该提案的主旨是确定递送这些编码序列的最佳质粒、肌内递送的最佳制剂以及在大型哺乳动物中实现保护的最佳注射方案和剂量。它汇集了Vical公司，该公司在过去12年中拥有先进的DNA疫苗接种技术，并拥有制造DNA疫苗商业产品所需的知识产权，以及俄亥俄州州立大学教授和研究人员Darrell Galloway博士，他推动了DNA疫苗对炭疽的使用。该提案还介绍了一个拥有这些临床前实验所需的专业知识、动物设施和试剂的学术实验室与一家小型生物技术公司在DNA疫苗开发方面的专家如何共同努力，将这种新的疫苗技术迅速推向临床。

DESCRIPTION (provided by applicant): This STTR grant proposal is for the development of a safe and efficacious Anthrax Toxin Vaccine. The present world-wide threat of the use of anthrax spores as a bioterrorist weapon in military theaters as well as on the general population has focused attention on the need for a more effective vaccine against anthrax. The recognition during the past few months that few members of the medical community have seen an anthrax infection in humans and therefore only a very few are equipped to diagnose and treat anthrax. The availablity of a safe and efficacious prophylactic vaccine would effectively neutralize this form of bioterrorist threat. Price, et al., have shown that a vaccine comprised of plasmid DNAs encoding detoxified protective antigen (PA) and lethal factor (LF) protects mice from an intravenous challenge using 5X the lethal dose of toxic protein. Based on this work and subsequent work (presented here) showing that a similar DNA vaccination protocol can protect rabbits from a more rigorous spore inhalation challenge, this grant proposes the pre-clincal work required to support testing of a DNA vaccine in human clinical trials. The work would advance an FDA approved plasmid DNA vector encoding the the PA or LF plasmids or a formulation combining the PA + LF plasmids through a series of experimental protocols to demonstrate the generation of a protective immunne response in both mice and rabbits. The thrust of this proposal is to determine the best plasmid to deliver these coding sequences, the best formulation for intramuscular delivery, and the best injection regime and dosage for achieving protection in a large mammal This work demonstrates the best use of STTR funding. It brings together Vical, the company which has advanced DNA vaccination technology over the past 12 years and holds the intellectural property required to make DNA vaccines commercial products, with Dr. Darrell Galloway, a professor at Ohio State University and a researcher who has advanced the use of DNA vaccines against anthrax. The proposal also presents how the combined efforts of an academic laboratory with the expertise, animal facilities, and reagents required for these pre-clinical experiments and a small biotechnology company expert in the development of DNA vaccines, can work together to quickly advance this novel vaccine technology into the clinic.