Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax

在这个更新申请中，我们建议继续我们的多学科方法来研究人类炭疽芽孢杆菌感染。我们认为炭疽杆菌是对我们社会最重大的威胁之一，是一种生物恐怖主义制剂，与它作为生物武器的用途不同。B.炭疽菌作为恐怖武器令人担忧的原因有以下几点：1)孢子在恶劣环境中寿命长且稳定；2)疫苗质量差，效力可疑，注射时间表繁琐，不提供给平民；3)没有有效的治疗方法；少数人死于一种罕见的外来疾病，就足以使我们的人民感到恐惧。事实上，这正是2001年美国邮政服务中心（US Postal Service Center）遭到攻击后发生的情况。

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.