Rapid Response Agents Against Filovirus Outbreaks Using Vectored Immunoprophylaxis

使用载体免疫预防针对丝状病毒爆发的快速反应剂

• 批准号: 9200868
• 负责人: Larry Zeitlin
• 金额: $ 24.02万
• 依托单位: MAPP BIOPHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9200868
• 关键词: Address; Animal Model; Animals; Antibodies; Bioterrorism; Categories; Cavia; Communicable Diseases; DNA; Democratic Republic of the Congo; Dengue Virus; Disease Outbreaks; Ebola Vaccines; Ebola virus; Enzyme-Linked Immunosorbent Assay; Epidemic; Europe; Filovirus; Gene Therapy Agent; Gene Transfer; Genes; Glycoproteins; Goals; Guinea; HIV; HIV Antibodies; HIV prevention trial; Head; Health Personnel; Human; Immunofluorescence Immunologic; Immunoprecipitation; In Vitro; Individual; Infection; Infectious Agent; Injection of therapeutic agent; International; Investigation; Kinetics; Liberia; Life; Macaca; Modeling; Monoclonal Antibodies; Mus; Passive Immunization; Pattern; Phase; Plasmids; Population; Prevention approach; Production; Reagent; Reporting; Sierra Leone; System; Technology; Testing; Therapeutic; Time; United States; Vaccines; Viral Hemorrhagic Fevers; Virus; Western Blotting; Work; abstracting; adeno-associated viral vector; base; clinical efficacy; efficacy evaluation; high risk; immunoprophylaxis; in vivo; man; mortality; mouse model; murine monoclonal antibody; nonhuman primate; optimism; prophylactic; public health emergency; response

Summarty / Abstract Vectored immunoprophylaxis, or antibody gene transfer for infectious disease, is a promising new strategy to provide protection against high risk infectious agents, supplementing vaccine and passive immunization efforts. It has been demonstrated to be effective against HIV and Dengue virus in animal models, and there is currently an ongoing human trial for HIV prevention in high-risk individuals with an adeno-associated viral vector (AAV) delivering the gene for a broadly neutralizing HIV antibody. We propose to expand these efforts to the filoviruses, starting with the Ebolavirus Zaire (EBOV). EBOV causes severe hemorrhagic fever, with a high mortality between 30 and 90%, depending on the virus. Although the recent EBOV epidemic appears to be waning, the outbreak was classified by the WHO as "an international public health emergency." In addition, Ebolavirus is a potential bioterrorism agent (Category A). While recent reports suggest optimism for an Ebola vaccine, these are early trials with much work to be done to prove efficacy, and to characterize the onset of protection and durability. Passive immunization has shown great promise against EBOV in a therapeutic setting, however, production capabilities are not yet available for protection of a large segment of the population, and passive immunization requires repeated administration if used in a prophylactic setting. As such, there is an ongoing need for increasing the repertoire of immunoprotectants such as vectored antibodies.

摘要/摘要 载体免疫预防，或用于传染病的抗体基因转移，是一种有前途的新策略， 提供针对高风险传染性病原体的保护，补充疫苗和被动免疫工作。 它已被证明是有效的抗艾滋病毒和登革热病毒的动物模型，目前有 一项正在进行的使用腺相关病毒载体（AAV）在高危人群中预防HIV的人体试验 传递一种广泛中和的HIV抗体的基因。我们建议扩大这些努力， 丝状病毒，从扎伊尔埃博拉病毒（EBOV）开始。EBOV引起严重的出血热， 死亡率在30%到90%之间，取决于病毒。虽然最近的EBOV流行似乎是 随着疫情逐渐减弱，世界卫生组织将此次疫情列为“国际公共卫生紧急事件”。“此外， 埃博拉病毒是一种潜在的生物恐怖主义制剂（A类）。虽然最近的报告显示埃博拉病毒的乐观情绪 疫苗，这些都是早期试验，有很多工作要做，以证明疗效，并表征发病 保护和耐用性。被动免疫在治疗EBOV方面显示出巨大的前景。 然而，在这种情况下，生产能力尚不足以保护大部分的 被动免疫如果用于预防性环境则需要重复施用。作为 因此一直需要增加免疫保护剂如载体化抗体的库。