Consortium for Immunotherapeutics against Emerging Viral Threats

针对新兴病毒威胁的免疫治疗联盟

• 批准号: 9924443
• 负责人: Erica Ollmann Saphire
• 金额: $ 714.34万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9924443
• 关键词: Address; Alphavirus; Antibodies; Antigen Targeting; Arenavirus; Arthritogenic; Biological Assay; Communicable Diseases; Computer Analysis; Computer Models; Computing Methodologies; Coupled; Culicidae; Data; Databases; Developed Countries; Developing Countries; Disease; Ebola; Ebola virus; Epidemic; Evolution; Family; Filovirus; Fostering; Goals; Hand; Health; Human; Immune; Immunotherapeutic agent; Lassa virus; Machine Learning; Mathematics; Mediating; Monoclonal Antibodies; Monoclonal Antibody Therapy; Movement; Multivariate Analysis; Nature; Populations at Risk; Primate Diseases; Reagent; Research Project Grants; Resources; Statistical Data Interpretation; System; Talents; Testing; Therapeutic; Therapeutic Monoclonal Antibodies; Translating; Translations; United States; Vaccines; Viral; Virus; Virus Diseases; base; biodefense; chikungunya; clinical development; design; experience; human monoclonal antibodies; improved; industry partner; innovation; insight; mosquito-borne; multidisciplinary; nonhuman primate; novel; pandemic disease; pathogen; programs; research study; structural biology; success; synergism; tool

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.

摘要：总体 该提议是针对新兴病毒疾病的免疫治疗药物的财团，解决了关键 通过建立学术行业合作伙伴关系来提高有效，完全人性， 基于抗体的免疫疗法针对新兴/重新出现病毒的三个主要家庭：LASSA病毒， 埃博拉病毒和其他丝状病毒，以及蚊子传播的α病毒，威胁着全球数百万。这 计划直接来自我们重要的初步数据（这些最大的数据，可用于这些家族 病毒），手头的治疗剂，多学科专业知识并展现出协作成功。包括在 拟议的CORTOR组合是：（1）唯一针对特有LASSA病毒的免疫治疗药物，具有 后期疾病的逆转和在受感染的非人类灵长类动物中的完全存活，（2）新型埃博拉病毒和泛 埃博拉病毒疗法也完全保护非人类灵长类动物免受疾病的侵害，并且由 全球财团的范式转移和综合分析，以及（3）急需的一流 反对在美国具有巨大流行潜力的重新出现的α病毒的治疗剂 和全球。这些多学科研究，建立在抗原的开创性结构生物学上 目标，包括不可知论，高通量FC分析和优化等创新，并与FV结合 增强效力和发展性的进化以及复杂的统计和计算分析 评估主要病原体家族的阈值和保护性相关的核心。在一起，我们 旨在了解哪些发现代表一般规则以及哪些数据是特定于每个病毒家族的。我们也是 旨在为尚不存在的抗体选择和优化提供精简系统，并建立一个 广泛适用的平台，用于对任何新型病原体出现的MAB发现和传递。这 LASSA的最新复兴，埃博拉病毒和其他重新出现的丝病毒的流行性以及 蚊子传播α病毒的全球运动有危险的主要人群，共同证明了 该计划开发和提出了对免疫治疗剂的巨大全球需求。