Core A: Protein Sciences

核心 A：蛋白质科学

• 批准号: 10425026
• 负责人: Neil King
• 金额: $ 95.84万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-02 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10425026
• 关键词: Antigen-Antibody Complex; Antigens; Area; B-Lymphocytes; Binding; Biological Assay; Bioreactors; Cell Separation; Collaborations; Complex; Coronavirus; Coronavirus spike protein; Cryoelectron Microscopy; Cyclic GMP; Development; Documentation; Ensure; Epitopes; Equipment; Fab Immunoglobulins; Formulation; Glycoproteins; Goals; HIV-1; Human Resources; Imaging Techniques; In Vitro; Influenza; Institutes; Institution; Laboratories; Lead; Medicine; Methods; Monoclonal Antibodies; Peptides; Process; Production; Protein Engineering; Protein Sortings; Proteins; Public Health; Quality Control; Reagent; Reference Standards; Research; Research Support; Resolution; Sarbecovirus; Science; Scientist; Serology; Speed; Structure; System; Technology Transfer; Testing; Time; Translating; Translations; Vaccine Design; Vaccines; Viral; X-Ray Crystallography; analytical method; base; betacoronavirus vaccine; clinical development; coronavirus vaccine; cost; design; experience; experimental study; flexibility; high throughput screening; immunogenicity; in vivo; industry partner; innovation; iterative design; method development; nanoparticle; polyclonal antibody; preclinical development; programs; protein structure function; receptor; scale up; structural biology; vaccine candidate

PROJECT SUMMARY – CORE A: PROTEIN SCIENCES Core A (Protein Sciences) will provide essential support to our Projects and Cores in three areas: protein production and characterization, high-resolution structure determination, and process development and technology transfer. Core A’s protein production and characterization efforts, led by Dr. Neil King and Lauren Carter, will leverage the extensive facilities and equipment at UW’s Institute for Protein Design (IPD) as well as its unique expertise in nanoparticle immunogens. Rigorous characterization and quality control testing will ensure the provision of high-quality antigens, nanoparticle immunogens, and protein-based reagents to support the scientific efforts of Projects 1 (Veesler), 2 (King), and 3 (Pulendran). Structure determination by both X-ray crystallography and cryo-electron microscopy will be led by Dr. David Veesler and will make use of state-of-the- art, in-house facilities including UW’s Arnold and Mabel Beckman Cryo-EM Center. High-resolution structures of designed antigens, nanoparticle immunogens, and antigen-antibody complexes will provide critical information to guide the iterative design of stabilized antigens and broadly protective vaccines in Project 2. Process development and technology transfer of our lead vaccine candidates (a pan-sarbecovirus vaccine at the end of Year 2 and a pan-betacoronavirus vaccine at the end of Year 5), led by Dr. Neil King and Lauren Carter, will build upon the IPD’s proven track record in translating innovative protein-based medicines and vaccines to industry partners. A dedicated team at the IPD will develop the methods and documentation for a comprehensive technology transfer package that will speed preclinical and clinical development of our broadly protective coronavirus vaccines.

项目摘要 – 核心 A：蛋白质科学 核心 A（蛋白质科学）将为我们的项目和核心在三个领域提供必要的支持：蛋白质 生产和表征、高分辨率结构测定以及工艺开发和 技术转让。由 Neil King 博士和 Lauren 领导的 Core A 蛋白质生产和表征工作 Carter 将利用华盛顿大学蛋白质设计研究所 (IPD) 的广泛设施和设备以及 其在纳米颗粒免疫原方面的独特专业知识。严格的表征和质量控制测试将确保 提供高质量的抗原、纳米颗粒免疫原和基于蛋白质的试剂来支持 项目 1 (Veesler)、2 (King) 和 3 (Pulendran) 的科学成果。通过 X 射线进行结构测定 晶体学和冷冻电子显微镜将由 David Veesler 博士领导，并将利用最先进的技术 艺术、内部设施，包括威斯康星大学阿诺德和梅布尔贝克曼冷冻电镜中心。高分辨率结构 设计的抗原、纳米颗粒免疫原和抗原抗体复合物将提供关键信息 指导项目2中稳定抗原和广泛保护性疫苗的迭代设计。流程 我们的主要候选疫苗（年底的泛沙病毒疫苗）的开发和技术转让 由 Neil King 博士和 Lauren Carter 领导的第 2 年和第 5 年年底的泛 β 冠状病毒疫苗将 建立在 IPD 在将创新的蛋白质药物和疫苗转化为 行业合作伙伴。 IPD 的一个专门团队将开发方法和文档，以实现全面的 技术转让包将加速我们广泛保护的临床前和临床开发 冠状病毒疫苗。