Rapid Response Agents Against Filovirus Outbreaks Using Vectored Immunoprophylaxis

摘要/摘要 载体免疫预防，或传染病抗体基因转移，是一种很有前途的新策略 提供针对高风险传染病的保护，补充疫苗和被动免疫努力。 它已被证明在动物模型中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携带腺相关病毒载体(AAV)的高危人群的HIV预防人体试验 传递一种广泛中和艾滋病毒抗体的基因。我们建议将这些努力扩大到 丝状病毒，从埃博拉病毒扎伊尔(EBOV)开始。EBOV引起严重出血热，具有很高的 死亡率在30%到90%之间，具体取决于病毒。尽管最近的EBOV疫情似乎是 疫情逐渐消退，世界卫生组织将其列为“国际突发公共卫生事件”。此外, 埃博拉病毒是潜在的生物恐怖主义病原体(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，有很多工作要做，以证明有效性，并表征发病 保护和耐用。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，还没有生产能力来保护很大一部分 如果在预防性环境中使用，被动免疫需要反复接种。AS 因此，需要不断增加免疫保护剂的保留量，如载体抗体。

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.