Poxvirus

痘病毒

• 批准号: 7678786
• 负责人: Stuart N. Isaacs
• 金额: $ 69.17万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7678786
• 关键词: Aerosols; Bioterrorism; Blood; Collaborations; Communities; Ectromelia; Emerging Communicable Diseases; Event; Funding; Goals; Human; Immune system; Immunocompromised Host; Immunoglobulins; Immunology; Immunotherapy; Infant; Infection; Infectious Ectromelia; Lead; Life; Modeling; Monkeypox; Morbidity - disease rate; Mosses; Mouse Pox Virus; Mus; Myron; Pathogenesis; Pennsylvania; Persons; Phage Display; Population; Populations at Risk; Poxviridae; Poxviridae Infections; Pregnant Women; Prevention; Principal Investigator; Probability; Proteins; Proteomics; Qualifying; Reagent; Research; Research Personnel; Research Project Grants; Respiratory System; Schools; Series; Smallpox; Smallpox Vaccine; Smallpox Viruses; Structure; Subunit Vaccines; System; Talents; Techniques; Technology; Testing; Therapeutic Intervention; United States National Institutes of Health; Universities; Vaccinated; Vaccination; Vaccines; Vaccinia; Vaccinia virus; Viral Pathogenesis; Viral Proteins; Virginia; Virus; Work; base; biodefense; experience; mortality; neutralizing antibody; nonhuman primate; prevent; programs; respiratory

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)

与Variola病毒的生物恐怖主义非常关注，因为（a）几乎整个世界人口是 易感性，因为停止了常规疫苗接种； （b）没有治疗； （c）气溶胶中的病毒 形式是稳定的； （d）该病毒是可以传播的人； （e）感染导致高发病率和 死亡。疫苗病毒（VV）疫苗接种是根除天花的关键因素。必要 疫苗接种W具有W的高危人群对于为天花的潜在威胁做准备是至关重要的 生物恐怖。然而，疫苗接种疫苗的并发症，尤其是在免疫功能低下的并发症 宿主，孕妇和婴儿对此策略施加了严重的限制。在过去的疫苗接种工作中， 这种并发症在美国通过从W的人类免疫球蛋白（VIG）处理 免疫人员。当前的VIG库存较低，在产生新的股票时，仍然有 严重依靠血液产品的缺点。因此，有迫切需要发展 治疗干预措施可抵消当前疫苗并开发更安全的疫苗的并发症。 作为中大西洋中部地区卓越生物性和新兴传染病卓越中心的一部分，我们 痘病毒研究项目的假设是，候选疫苗和新疗法可以由 理解和靶向由体液和先天免疫系统认可的痘病毒蛋白。做 我们将： 1。开发针对天花（Variola）病毒的亚基疫苗（Cohen/Eisenberg/Friedman，U。Penn） 2。确定中和抗体的新目标（Isaacs，U.Penn） 3。使用蛋白质组学方法（Lambris，U.Penn）确定VIG的目标 4。在小鼠中开发一个源自鼻病毒挑战系统，作为天花发病机理的模型和 预防（Braciale，美国弗吉尼亚州）