Poxvirus

天花病毒的生物恐怖主义引起了极大的关注，因为（a）几乎整个世界人口都在 由于常规疫苗接种已停止，因此易感;（B）没有治疗方法;（c）气溶胶中的病毒 形式稳定;（d）病毒可人际传播;及（e）感染导致高发病率， mortality.接种牛痘病毒（VV）是根除天花的关键因素。的必要性 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 宿主、孕妇和婴儿严重限制了这一策略。在过去的疫苗接种工作中， 这种并发症在美国用从W. 免疫的人。目前VIG的库存较低，虽然新的库存正在产生，但仍有 依赖血液制品的严重缺点。因此，迫切需要发展 治疗干预措施，以应对目前疫苗的并发症，并开发一种更安全的疫苗。 作为大西洋中部地区生物防御和新兴传染病卓越中心的一部分， 痘病毒研究项目的假设是，疫苗候选人和新的治疗方法可以开发， 理解和靶向由体液和先天免疫系统识别的痘病毒蛋白。做 我们将： 1.开发针对天花病毒的亚单位疫苗（Cohen/Eisenberg/Friedman，U.佩恩） 2.鉴定中和抗体的新靶标（Isaacs，U.佩恩） 3.使用蛋白质组学方法鉴定VIG的靶点（Lambris，U.佩恩） 4.在小鼠中开发一种肢脱病病毒攻击系统作为天花发病机制的模型， 预防（Braciale，U.弗吉尼亚州）

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)