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 载体免疫预防或针对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源的保护，补充疫苗和被动免疫工作。 它已在动物模型中被证明对艾滋病毒和登革热病毒有效，目前有 一项正在进行的针对使用腺相关病毒载体（AAV）的高危人群预防艾滋病毒的人体试验 传递广泛中和艾滋病毒抗体的基因。我们建议扩大这些努力 丝状病毒，首先是扎伊尔埃博拉病毒（EBOV）。埃博拉病毒会引起严重的出血热，发病率很高 死亡率在 30% 到 90% 之间，具体取决于病毒。尽管最近的埃博拉病毒疫情似乎 随着疫情的减弱，世界卫生组织将疫情列为“国际突发公共卫生事件”。此外， 埃博拉病毒是一种潜在的生物恐怖主义媒介（A 类）。虽然最近的报告表明人们对埃博拉病毒持乐观态度 疫苗，这些都是早期试验，需要做很多工作来证明功效并描述疾病发作的特征 保护和耐用性。被动免疫在治疗埃博拉病毒方面显示出巨大的前景 然而，目前还没有生产能力来保护大部分 如果用于预防性环境，被动免疫需要重复施用。作为 因此，持续需要增加免疫保护剂的种类，例如载体抗体。