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提供三个领域的基本支持：蛋白质 生产和表征，高分辨率结构确定以及过程开发以及 技术转移。核心A的蛋白质生产和表征工作，由尼尔·金博士和劳伦领导 卡特（Carter）将利用威斯康星大学蛋白质设计研究所（IPD）的广泛设施和设备以及 它在纳米颗粒免疫原中的独特专业知识。严格的特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）的科学努力。两种X射线的结构测定 晶体学和冷冻电子显微镜将由David Veesler博士领导，并将利用最新 艺术，内部设施，包括西澳大学的Arnold和Mabel Beckman Cryo-Em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 在项目2中指导稳定抗原和广泛保护的疫苗的迭代设计。 我们的铅疫苗候选物的开发和技术转移（泛 - 萨尔贝病毒疫苗结束时 由尼尔·金（Neil King）博士和劳伦·卡特（Lauren Carter）领导的第5年级和pan-betacoronavirus疫苗，威尔 基于IPD在将创新蛋白质的药物和疫苗转化为IPD的良好往绩之下 行业合作伙伴。 IPD的专门团队将开发全面的方法和文档 技术转移包将加快我们广泛保护的临床前和临床开发 冠状病毒疫苗。