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: 10199909
• 负责人: Erica Ollmann Saphire
• 金额: $ 268.88万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-27 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10199909
• 关键词: 2019-nCoV; Address; Affinity; Antibodies; Antibody Therapy; Antibody-mediated protection; Antigen-Antibody Complex; Area; Binding; Biological Assay; Blinded; Characteristics; Clinical; Clinical Research; Complement; Complex; Coronavirus; Cryoelectron Microscopy; Data; Data Set; Databases; Engineering; Ensure; Epitopes; FAIR principles; Funding; Geometry; Half-Life; Human; Immunoglobulin G; Immunotherapeutic agent; In Vitro; International; Knowledge; Maps; Mechanics; Mediating; Membrane; Myeloid Cells; Participant; Population; Predisposition; Proteins; Race; Research Project Grants; Risk; Sampling; Serologic tests; Side; Site; Speed; Structure; Surface; Surveys; System; Therapeutic; Therapeutic antibodies; Time; Transgenic Model; United States National Institutes of Health; Variant; Viral; clinical candidate; experimental study; mouse model; neonatal Fc receptor; next generation; novel; programs; therapeutic candidate; tool

ABSTRACT We recently galvanized the Coronavirus Immunotherapeutic Consortium, CoVIC, an international effort to conduct side-by-side analyses of leading therapeutic antibody candidates against the SARS-CoV-2 Spike protein contributed by a range of large and small companies and academic labs on multiple continents. CoVIC provides an opportunity for side-by-side analysis of the leading therapeutic candidates under the same assay conditions, as well as real-time collaborative assembly of a broader, deeper dataset on the activities and potencies of antibodies against SARS-CoV-2 than could be assembled by any single discovery effort alone. The currently funded CoVIC studies focus largely on characteristics of the Fab region of the IgG therapeutic: binding and mechanical neutralization, and analyze only spike from the original Wuhan reference strain of SARS-CoV- 2. The proposed supplement will provide support for critical components that are currently missing from CoVIC but which are needed to accelerate clinical advancement of antibodies that will be safe, efficacious and offer durable protection. We will determine Fc-mediated activities of the therapeutic antibodies, the likelihood or risk of enhancement from clinical candidates, and which epitopes and sites of and susceptibility to mutagenic escape. The resulting body of information will inform early and next-generation antibody therapies and will ensure that therapeutics are known which are responsive to emerging viral variants.

摘要 我们最近激励了冠状病毒免疫联盟，CoVIC，一项国际努力， 对针对SARS-CoV-2 Spike的主要治疗性候选抗体进行并行分析 蛋白质由一系列大小公司和多个大陆的学术实验室贡献。乔维奇 提供了在相同测定下并行分析主要治疗候选物的机会 条件，以及实时协作组装更广泛，更深入的活动数据集， 抗体的效力比任何单一的发现努力都要强大。的 目前资助的CoVIC研究主要集中在IgG治疗剂的Fab区的特征： 和机械中和，只分析SARS冠状病毒武汉参考毒株的刺突， 2.拟议补充将为CoVIC目前缺失的关键组件提供支持 但是需要它们来加速抗体的临床进展，所述抗体将是安全的、有效的， 持久的保护。我们将确定Fc介导的治疗性抗体的活性， 从临床候选人的增强，以及哪些表位和网站和诱变逃逸的易感性。 由此产生的信息将为早期和下一代抗体疗法提供信息，并确保 已知对出现的病毒变体有反应的治疗剂。