Consortium for Immunotherapeutics against Emerging Viral Threats

摘要：总体 这项名为针对新出现的病毒疾病的免疫疗法联盟的提案解决了一个关键的 通过建立学术和行业合作伙伴关系，推动有效的、完全人性化的、 以抗体为基础的免疫疗法针对三个主要的新出现/重新出现的病毒家族：拉萨病毒， 埃博拉病毒和其他丝状病毒，以及蚊子传播的甲型病毒，威胁着全球数百万人。这 该计划直接来自我们重要的初步数据(这些家庭可用的最大数据 病毒)，手头的治疗方法，多学科的专业知识，并展示了合作的成功。包括在 拟议的CETR组合是：(1)针对地方性Lassa病毒的唯一可用的免疫疗法， 逆转晚期疾病和在受感染的非人类灵长类动物中完全存活，(2)新的埃博拉和泛 埃博拉病毒疗法也完全保护非人类灵长类动物免受疾病侵袭，这是由 全球财团的范式转变和全面分析，以及(3)急需的、一流的 针对在美国具有巨大流行潜力的重新出现的甲型病毒的治疗 在全球范围内。这些多学科研究建立在抗原结构生物学的开创性基础上 目标包括不可知的高吞吐量光纤通道分析和优化等创新，以及FV 进化以增强潜力和发展能力，以及复杂的统计和计算分析 核心是评估主要病原体家族的保护阈值和相关性。在一起，我们 目的了解哪些发现代表一般规律，以及哪些数据针对每个病毒家族。我们也 旨在为抗体选择和优化提供尚不存在的简化系统，并建立一种 当新病原体出现时，为mAb发现和提供广泛适用的平台。这个 最近拉萨病毒的卷土重来，埃博拉病毒和其他重新出现的丝状病毒的流行性质，以及 蚊媒甲型病毒全球传播的主要危险人群共同证明 由该计划开发和推进的全球对免疫疗法的巨大需求。

SUMMARY: OVERALL This proposal, Consortium for Immunotherapeutics Against Emerging Viral Diseases, addresses a critical gap in the biodefense portfolio by building an academic-industry partnership to advance effective, fully human, antibody-based immunotherapeutics against three major families of emerging/re-emerging viruses: Lassa virus, Ebola and other Filoviruses, and mosquito-transmitted Alphaviruses that threaten millions worldwide. This program follows directly from our significant body of preliminary data (the largest available for these families of viruses), therapeutics in hand, multidisciplinary expertise, and demonstrated collaborative success. Included in the proposed CETR portfolio are: (1) the only available immunotherapeutics against endemic Lassa virus, with reversal of late-stage disease and complete survival in infected non-human primates, (2) novel Ebola and pan- ebolavirus therapeutics that also completely protect non-human primates from disease, and that were built by the paradigm-shifting and comprehensive analysis of a global consortium, and (3) much needed, first-in-class therapeutics against the re-emerging alphaviruses that have tremendous epidemic potential in the United States and around the globe. These multidisciplinary studies, founded upon pioneering structural biology of the antigen targets, include innovations such as agnostic, high-throughput Fc profiling and optimization, coupled with Fv evolution to enhance potency and developability, as well as a sophisticated statistical and computational analysis core to evaluate thresholds and correlates of protection across the major families of pathogens. Together, we aim to understand what findings represent general rules and what data are specific to each virus family. We also aim to provide streamlined systems for antibody choice and optimization that do not yet exist, and to build a broadly applicable platform for mAb discovery and delivery against any novel pathogen as they emerge. The recent resurgence of Lassa, the epidemic nature of Ebola virus and other re-emerging filoviruses, as well as the major population at risk by global movement of mosquito-borne alphaviruses together demonstrate the tremendous global need for immunotherapeutics developed and advanced by this program.