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 这项提案，针对新发病毒性疾病的免疫治疗联盟，解决了一个关键问题， 通过建立学术界与工业界的伙伴关系，以促进有效的，完全人性化的， 基于抗体的免疫治疗剂针对三种主要的新出现/再出现病毒家族：拉沙病毒， 埃博拉病毒和其他丝状病毒，以及蚊子传播的甲病毒，威胁着全球数百万人。这 该计划直接来自我们大量的初步数据（这些家庭的最大可用数据）。 病毒），治疗方法在手，多学科的专业知识，并展示了合作的成功。列入 建议的CETR组合是：（1）唯一可用的抗地方性拉沙病毒的免疫治疗药物， 在感染的非人灵长类动物中逆转晚期疾病和完全存活，（2）新型埃博拉病毒和泛- 埃博拉病毒治疗，也完全保护非人类灵长类动物免受疾病， 全球联盟的范式转变和全面分析，以及（3）急需的一流 针对在美国具有巨大流行潜力的重新出现的甲病毒的治疗方法 和地球仪的周围。这些多学科的研究，建立在开创性的结构生物学的抗原 目标，包括创新，例如不可知的、高通量的Fc分析和优化，以及Fv 进化以增强效力和可开发性，以及复杂的统计和计算分析 核心，以评估阈值和相关的保护跨主要家庭的病原体。一起我们 旨在了解哪些发现代表一般规律，哪些数据是每个病毒家族特有的。我们也 旨在为抗体选择和优化提供尚不存在的流线型系统，并建立一个 广泛适用的mAb发现和递送平台，以对抗任何新出现的病原体。的 最近拉沙热死灰复燃，埃博拉病毒和其他重新出现的丝状病毒的流行性质，以及 全球蚊媒甲病毒传播的主要风险人群共同证明， 全球对该计划开发和推进的免疫治疗药物的巨大需求。