Combinatorial vaccines against anthrax and plague

描述(由申请人提供)：直到最近，炭疽病还主要是畜牧业工作人员和军事规划者关注的问题，他们担心炭疽孢子可能被用作生物战的制剂。将炭疽菌用作平民人口的生物恐怖主义制剂在理论上是一种风险，尤其是发现某些无赖国家(特别是伊拉克、叙利亚和中国)已经或正在试图开发炭疽菌或其他生物制剂作为大规模杀伤性武器，9·11事件后炭疽孢子的释放导致5名平民死亡，18人感染，并要求30,000多人接受预防性抗生素治疗。这次活动还强调需要改进疫苗，使之适合于平民和军人在接触前或接触后对潜在生物恐怖主义制剂进行免疫，包括炭疽病和鼠疫，将来自不同微生物的保护性抗原与可能用作生物战/生物恐怖主义制剂的平民或军人相结合的疫苗将是有利的，因为它们既扩大了这类疫苗的覆盖面，又减少了免疫的总次数。第一个要检验的逻辑组合是炭疽杆菌的RPA和鼠疫杆菌的F1-V，因为它们分别被证明可以诱导保护性反应。联合疫苗以减少免疫次数和增加疫苗覆盖率在疫苗开发中并不是一个新概念，DTP和MMR等联合疫苗已经使用了很多年。然而，在临床试验和实验室测试中都观察到了几个联合疫苗单独成分之间的免疫干扰的例子。因此，我们建议研究由RPA和F1-V组成的联合疫苗的潜力，具体目标是确定疫苗成分之间的协同或干扰。对于这一应用，我们建议解决一些相互关联的问题，即使用含有RPA和F1-V作为免疫原的联合疫苗进行免疫，以预防炭疽和鼠疫。

DESCRIPTION (provided by applicant): Until recently, anthrax was primarily a concern of individuals working in animal husbandry and military planners concerned about the potential use of anthrax spores as an agent of biological warfare. The use of anthrax as an agent of bioterrorism on civilian populations was a theoretical risk, heightened by the discovery that certain rogue nations (notably Iraq, Syria, and China) either had developed or were attempting to develop anthrax or other biologic agents as a weapon of mass destruction, The post- September 11 release of anthrax spores resulted in five civilian deaths, eighteen infections, and required that more than 30,000 individuals to undergo prophylactic antibiotic therapy. This event also highlighted the need for improved vaccines that would be appropriate for pre- or post- exposure immunization of civilian and military populations against potential bioterrorism agents, including anthrax and plague, Vaccines combining protective antigens from different microorganisms with potential for use against civilian or military populations as biological warfare/biological terrorism agents would be advantageous because they would both broaden the coverage of such vaccines and reduce the overall number of immunizations. The first logical combination to examine would be rPA from B. anthracis and F1-V from Y. pestis since they have individually been shown to induce protective responses. Combining vaccines to decrease the number of immunizations and to increase vaccine coverage is not a new concept in vaccine development and combination vaccines such as DTP and MMR have been used for many years. However, several examples of immunologic interference between individual components of combination vaccines have been observed both in clinical trials and in laboratory tests. We are therefore proposing to examine the potential of a combined vaccine consisting of rPA and F1-V with the specific objective of determining synergy or interference between the vaccine components. For this application, we propose to address a number of interrelated questions regarding immunization with a combined vaccine containing rPA and F1-V as immunogens to protect against anthrax and plague.