Poxvirus

与天花病毒有关的生物恐怖主义令人极为关切，因为：(A)几乎全世界人口都是 由于停止常规疫苗接种而易受感染；(B)没有治疗方法；(C)气雾剂中的病毒 (D)病毒可在人与人之间传播；及(E)感染导致高发病率及 死亡率。接种牛痘病毒是根除天花的关键因素。有必要 为高危人群接种W疫苗是预防天花潜在威胁的关键 生物恐怖主义。然而，公认的牛痘疫苗接种并发症，特别是在免疫功能低下的情况下 宿主、孕妇和婴儿对这一策略施加了严重的限制。在过去的疫苗接种工作中， 在美国，这些并发症是用从W获得的人牛痘免疫球蛋白(VIG)治疗的 接种疫苗的人。VIG目前的库存较低，虽然正在产生新的库存，但仍有 依赖血液产品的严重缺陷。因此，迫切需要发展 治疗干预措施，以对抗当前疫苗的并发症，并开发更安全的疫苗。 作为中大西洋生物防御和新发传染病卓越区域中心的一部分，我们的 痘病毒研究项目的假设是，候选疫苗和新疗法可以通过以下方式开发 理解和定位体液免疫系统和先天免疫系统识别的痘病毒蛋白。去做 为此，我们将： 1.开发一种针对天花(天花)病毒的亚单位疫苗(科恩/艾森伯格/弗里德曼，宾夕法尼亚大学) 2.确定中和抗体的新靶点(Isaacs，U.Penn) 3.使用蛋白质组学方法确定VIG的靶标(兰布里斯，宾夕法尼亚大学) 4.在小鼠中建立一种蜕皮病病毒攻击系统，作为天花发病机制的模型和 预防(美国弗吉尼亚州布雷西亚尔)

Bioterrorism with variola virus is of immense concern because (a) virtually the entire world population is susceptible since routine vaccination was discontinued; (b) there are no treatments; (c) the virus in aerosol form is stable; (d) the virus is transmissible person-to-person; and (e) infection results in high morbidity and mortality. Vaccination with vaccinia virus (VV) was a key factor in eradicating smallpox. The necessity to vaccinate an at-risk population with W is central to preparing for the potential threat of smallpox bioterrorism. However recognized complications of vaccinia vaccination, especially in immunocompromised hosts, pregnant women, and infants impose serious limitations of this strategy. In past vaccination efforts, such complications were treated in the U.S. with human vaccinia immune globulin (VIG) obtained from W immunized people. Current stocks of VIG are low, and while new stocks are being generated, there are still serious drawbacks to relying on a blood product. Consequently, there is a critical need to develop therapeutic interventions to counter complications from the current vaccine and to develop a safer vaccine. As part of the mid-Atlantic Regional Center of Excellence in Biodefense & Emerging Infectious Diseases, our poxvirus research project's hypothesis is that vaccine candidates and new therapies can be developed by understanding and targeting poxvirus proteins recognized by the humoral and innate immune system. To do this we will: 1. Develop a subunit vaccine against smallpox (variola) virus (Cohen/Eisenberg/Friedman, U. Penn) 2. Identify new targets of neutralizing antibody (Isaacs, U. Penn) 3. Identify the targets of VIG using a proteomics approach (Lambris, U. Penn) 4. Develop an ectromelia virus challenge system in the mouse as a model of smallpox pathogenesis and prevention (Braciale, U. Virginia)