Consortium for Immunotherapeutics Against Viral Hemorrhagic Fevers

A类丝状病毒和沙粒病毒引起严重和快速进展的出血热， 没有具体的治疗方法或疫苗。在可能的暴露前后治疗中， 经过审查，单克隆抗体目前被认为是最有效的，提供了最长的窗口， 暴露后治疗，并且由于安全性、可用性和 功效在过去的一年里，我们团队的成员首先确定了特定的抗体和鸡尾酒， 抗体，提供有效的暴露后保护，对埃博拉病毒和拉沙病毒在多个 动物模型我们将翻译这些疗法，并填补针对其他疾病的抗体的关键资源缺口。 致病性丝状病毒（苏丹、马尔堡和本迪布焦）和沙粒病毒（Lujo、Machupo、朱宁等）。这 该提案描述了一个由学术和工业研究人员组成的大型多学科联盟。我们有 收集了约315个针对丝状病毒的单克隆抗体和约100个针对 沙粒病毒这是有史以来为这些病毒组装的最大的抗体库， 已知的有效抗体。该联盟包括三个BSL 4实验室的主任-在职专家 暴露疗法开发和评估;高通量和人抗体领域的其他领导者 2012年，通过获得独特的大型人类疫情幸存者群体进行发现和分析; 结构生物学家对丝状病毒和沙粒病毒糖蛋白有深入的了解，能够绘制出 在项目过程中，几乎所有抗体池中的表位; 是大规模生产和评估人类治疗药物的专家。我们的财团是开放的 所有的研究者和他们希望提供的抗体。我们将提供一个公开、全面和 明确分析哪些抗体对这些抗体最有效，以及为什么，哪些抗体 可以组合以获得最大的协同作用，为什么，以及哪些表位导致广谱反应性。的 我们的首要目标是发展基于单克隆抗体的免疫产品，以满足治疗需求 针对这些病毒家族，并在第5年前提交一份或多份研究性新药申请。

Category A filoviruses and arenaviruses cause severe and rapidly progressing hemorrhagic fever, for which no specific treatments or vaccines are available. Among the possible pre- and post-exposure treatments vetted, monoclonal antibodies are currently thought to be the most effective, provide the longest window for post-exposure treatment, and be most likely to achieve FDA approval for reasons of safety, availability and efficacy. In the last year, members of our team were first to identify specific antibodies and cocktails of antibodies that confer effective post-exposure protection against Ebola virus and Lassa virus in multiple animal models. We will translate these therapies and fill critical resource gaps in antibodies against other pathogenic filoviruses (Sudan, Marburg and Bundibugyo) and arenaviruses (Lujo, Machupo, Junin, etc.). this proposal describes a large, multidisciplinary consortium from academic and industrial investigators. We have gathered -315 monoclonal antibodies against the filoviruses and -100 monoclonal antibodies against the arenaviruses. These are the largest antibody pools ever assembled for these viruses and include the most potent antibodies known. The consortium includes directors of three BSL4 laboratories - experts in post exposure therapeutic development and evaluation; other leaders in high-throughput and human antibody discovery and analysis with access to unique, large cohorts of human survivors of outbreaks in 2012; structural biologists with intimate knowledge of the filovirus and arenavirus glycoproteins able to map the epitope of nearly every antibody in the pools during the course of the project; and industrial scientists who are experts in large-scale production and evaluation of therapeutics for human use. Our consortium is open to all investigators and to all antibodies they wish to contribute. We will provide a public, comprehensive and definitive analysis of which antibodies are most effective against these antibodies and why, which antibodies can be combined for greatest synergy and why, and which epitopes lead to broad-spectrum reactivity. The over-arching goal is to advance mAb-based immunotherapeutic products to fill the need for treatments against these families of viruses and to file one or more Investigational New Drug applications by year 5.