Combinatorial vaccines against anthrax and plague

炭疽和鼠疫组合疫苗

• 批准号: 6727477
• 负责人: JOHN D CLEMENTS
• 金额: $ 31.35万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6727477
• 关键词: Bacillus anthracis; Cercopithecidae; Yersinia pestis; Yersinia pestis disease; anthrax; anthrax vaccines; antibody neutralization test; antigen antibody reaction; bacterial vaccines; bioterrorism /chemical warfare; blood tests; combination chemotherapy; diagnostic respiratory lavage; drug administration rate /duration; drug administration routes; drug adverse effect; drug screening /evaluation; enzyme linked immunosorbent assay; laboratory mouse; nonhuman therapy evaluation

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.

描述（申请人提供）：直到最近，炭疽主要是畜牧业工作人员和军事规划人员担心炭疽孢子可能用作生物战剂的问题。使用炭疽作为对平民人口的生物恐怖主义的代理人是一种理论上的风险，由于发现某些流氓国家（特别是伊拉克、叙利亚和中国）要么已经开发或正在试图开发炭疽或其他生物制剂作为大规模杀伤性武器，911后炭疽孢子的释放导致5名平民死亡，18人感染，并要求三万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，使之适合于平民和军人在接触前或接触后对潜在的生物恐怖主义制剂，包括炭疽和鼠疫进行免疫，结合来自不同微生物的保护性抗原的疫苗，有可能作为生物战剂用于平民或军事群体/生物恐怖主义制剂将是有利的，因为它们既可以扩大此类疫苗的覆盖范围，又可以减少免疫接种的总数。要检查的第一个逻辑组合是来自B的rPA。anthracis和Y.鼠疫，因为它们已被单独显示出诱导保护性反应。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，并且联合疫苗如百白破和麻腮风疫苗已使用多年。然而，在临床试验和实验室试验中均观察到了联合疫苗的单个组分之间存在免疫学干扰的几个实例。因此，我们建议检查由rPA和F1-V组成的联合疫苗的潜力，具体目的是确定疫苗组分之间的协同作用或干扰。对于这个应用程序，我们建议解决一些相互关联的问题，关于免疫接种含有rPA和F1-V作为免疫原，以防止炭疽和鼠疫的联合疫苗。