Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax

在这份续签申请中，我们建议继续我们的多学科方法来研究人类中的炭疽杆菌感染。我们认为炭疽杆菌是作为生物恐怖分子对我们社会的最大威胁之一，有别于将其用作生物武器。炭疽杆菌作为恐怖武器令人担忧，原因有几个：1)孢子寿命长，在恶劣环境中稳定；2)疫苗质量差，效力可疑，注射程序繁琐，不提供给平民；3)这种疾病没有有效的治疗方法；4)一种罕见的外来疾病造成少量死亡，足以在我们的人口中造成恐惧。事实上，这正是2001年美国邮政服务中心遇袭后发生的事情。 我们的应用程序建立在以前资助的U19基础上，用于研究人类和非人类灵长类动物对炭疽杆菌感染和免疫的反应。在第一次赠款期间，我们建立了一个拥有非凡的物质和智力资产以及一流的基础设施的组织。我们组建的团队富有成效，互动性很强，在免疫学方面拥有令人敬畏的背景。我们的团队包括四个不同机构的教职员工、研究员、技术人员、兽医人员和其他支持人员：俄克拉荷马医学研究基金会、俄克拉荷马大学、现在的芝加哥大学和波士顿大学。申请包括五个科学项目、三个技术项目和两个核心设施(以及行政和教育核心)。我们从各个方面着手解决这个问题：主要在内部开发的强大的实验模型，疫苗遗传学和疫苗效力的新方法，几个宿主反应问题，外毒素的研究，以及两种新的令人兴奋的治疗方法。 总体而言，我们相信，四年的供资使我们处于具有竞争力的地位，能够利用我们第一个周期的调查结果，在未来五年取得实质性进展。

In this renewal application we propose to continue our multidisciplinary approach to the study of Bacillus anthracis infections in humans. We view B. anthracis as one of the most significant threats to our society as a bioterrorist agent, distinct from its use as a biological weapon. B. anthracis is alarming as a weapon of terror for several reasons: 1) the spore is long-lived and stable in harsh environments; 2) the vaccine is poor, of questionable efficacy, has a cumbersome injection schedule, and is not provided to civilians; 3) there are no effective treatments for the disease; 4) a small number of deaths from a rare and thus exotic disease is sufficient to cause terror in our population. Indeed, this is exactly what happened after the US Postal Service Center attacks in 2001. Our application builds on a previously funded U19 to study the human and non-human primate response to B. anthracis infections and immunizations. During the first grant period, we built an organization with remarkable physical and intellectual assets and a superb infrastructure. The group we assembled is productive, highly interactive and has a formidable background in immunology. Our group includes faculty, fellows, technicians, veterinary staff and other support staff at four different institutions: The Oklahoma Medical Research Foundation, The University of Oklahoma, and now The University of Chicago, and Boston University. The application contains five Scientific Projects, three Technical Projects and two Core Facilities (along with Administrative and Educational cores). We attack the problem from every direction: powerful experimental models largely developed in house, a novel approach to vaccine genetics and vaccine efficacy, several host-response issues, studies of the exotoxins, and two novel and exciting therapeutic approaches. Overall, we are confident that the four years of funding puts us in a competitive position to exploit the findings of our first cycle to make substantive advances in the next five years.