Combinatorial vaccines against anthrax and plague

描述（由申请人提供）：直到最近，炭疽主要是畜牧业工作者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一种剂。从理论上说，将炭疽作为对平民进行生物恐怖主义的一种手段是一种风险，而发现某些无赖国家（特别是伊拉克、叙利亚和中国）已经或正在开发或试图开发炭疽或其他生物制剂作为大规模杀伤性武器，更是加剧了这种风险。9月11日之后，炭疽孢子的释放导致5名平民死亡，18人感染，并要求3万多人接受预防性抗生素治疗。这一事件还突出表明，需要改进疫苗，使其适用于平民和军人在接触前或接触后接种疫苗，以防范潜在的生物恐怖主义剂，包括炭疽和鼠疫。将来自不同微生物的保护性抗原结合在一起，并有可能作为生物战/生物恐怖主义剂用于平民或军事人口的疫苗将是有利的，因为它们既可以扩大这类疫苗的覆盖范围，又可以减少免疫接种的总次数。首先要检查的合乎逻辑的组合将是来自炭疽杆菌的rPA和来自鼠疫杆菌的F1-V，因为它们已分别被证明可诱导保护性反应。联合疫苗以减少免疫接种次数和增加疫苗覆盖率并不是疫苗开发中的新概念，百白破和MMR等联合疫苗已使用多年。然而，在临床试验和实验室试验中观察到联合疫苗的个别成分之间存在免疫干扰的几个例子。因此，我们建议研究由rPA和F1-V组成的联合疫苗的潜力，其具体目标是确定疫苗成分之间的协同作用或干扰。对于这一应用，我们建议解决一些与含有rPA和F1-V作为免疫原的联合疫苗免疫有关的相关问题，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.