A Flexible High-Throughput Immunological Assay to Support Next-Generation Influenza Vaccine Studies

灵活的高通量免疫分析支持下一代流感疫苗研究

• 批准号: 10655239
• 负责人: George B Sigal
• 金额: $ 84.21万
• 依托单位: MESO SCALE DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-03 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655239
• 关键词: Acceleration; Address; Adenovirus Vector; Adopted; Animals; Antibodies; Antibody Diversity; Antibody Response; Antigens; Assessment tool; Benchmarking; Biological; Biological Assay; Birds; Blocking Antibodies; Blood; COVID-19; COVID-19 vaccine; Clinical; Clinical Research; Community Developments; Confidential Information; Cultured Cells; Detection; Development; Diagnostic; Epitopes; Erythrocytes; Evaluation; Government; Hemagglutination; Hemagglutinin; Human; Immune; Immune Evasion; Immune system; Immunoglobulin A; Immunoglobulin G; Immunology; Immunology procedure; Infection; Influenza; Influenza Hemagglutinin; Influenza vaccination; Label; Measurement; Measures; Messenger RNA; Methods; Michigan; Modality; Mutation; Pathway interactions; Persons; Phase; Preparation; Procedures; Process; Proteins; Protocols documentation; Qualifying; Quality Control; Reagent; Recombinants; Respiratory Tract Infections; Running; Sampling; Serology test; Sialic Acids; Site; Streptococcus pneumoniae; Translational Research; Update; Vaccination; Vaccines; Validation; Viral; Virus Diseases; Work; antibody test; assay development; commercialization; cross immunity; flexibility; flu; immunogenicity; improved; influenza infection; influenza virus vaccine; innovation; interest; manufacture; nanoparticle; next generation; novel vaccines; pandemic potential; performance tests; product development; programs; research and development; respiratory; sialic acid-binding lectin; success; technology platform; time use; tool; vaccine development; vaccine effectiveness; vaccine trial

Our objective is to develop better assays for measuring antibodies produced in people after influenza infection or vaccination. We’ll develop assays that measure total antibody responses, and assays that specifically measure the antibodies responsible for protection from infection. By using high-throughput multiplexed formats employing reagents that can be prepared and stored in large lots, the assays will address many of the practical limitations of current gold standard methods like the hemagglutination inhibition assay (HAI) and the viral micro- neutralization (MN) assay. The assays will use the Meso Scale Diagnostics® (MSD) electrochemiluminescence (ECL) assay platform, which has been widely adopted for qualification of COVID-19, pneumococcal and other vaccines. The assays will use multi-well plates with arrays of influenza hemagglutinin (HA) in each well to support the simultaneous measurement of antibodies against the strains represented in a vaccine, and to analyze cross-protection against other strains of interest. A set of detection reagents and assay formats will be developed that, when used with the antigen array component, will support a range of measurement modalities. These include the measurement of (i) antibodies that block the ability of each antigen to recognize sialic acid (SA) modified host proteins; (ii) total IgG and/or IgA against each antigen (in blood or respiratory samples); and (iii) antibodies recognizing pre-selected universal epitopes. Through this work, we will provide important tools for accelerating the development of new influenza vaccines. The phased UH2/UH3 program will include the following main components. In the UH2 feasibility/early development phase we will develop and optimize the required assay reagents needed to measure antibody responses to 10 recent vaccine strains, as well as several historical human strains and potentially pandemic avian strains. In this phase, we will also optimize the assay formats and assemble sample sets for later validation work. In the UH3 validation phase, we will establish manufacturing procedures for producing assay kits to conduct the proposed assay methods, and validate performance by testing well-characterized sample sets and comparing our results to established gold standard methods. †The sections on documents contained in this proposal that are marked with an asterisk contain proprietary/confidential information that MSD requests not be released to persons outside the Government, except for purposes of review and evaluation.

我们的目标是开发更好的检测方法来测量流感感染后人体内产生的抗体 或接种疫苗。我们将开发测量总抗体反应的测定法，以及专门针对 测量负责防止感染的抗体。通过使用高通量多路复用格式 使用可以大批量制备和储存的试剂，这些测定将解决许多实际问题 当前金标准方法的局限性，如血凝抑制测定（HAI）和病毒微量检测 中和（MN）测定。该检测将使用 Meso Scale Diagnostics® (MSD) 电化学发光 (ECL) 检测平台，已广泛应用于 COVID-19、肺炎球菌和其他疾病的鉴定 疫苗。该检测将使用多孔板，每孔中都有流感血凝素 (HA) 阵列 支持同时测量针对疫苗中所代表菌株的抗体，并 分析针对其他感兴趣菌株的交叉保护。一套检测试剂和测定格式将 开发出当与抗原阵列组件一起使用时，将支持一系列测量方式。 其中包括测量 (i) 阻断每种抗原识别唾液酸能力的抗体 (SA) 修饰的宿主蛋白； (ii) 针对每种抗原的总 IgG 和/或 IgA（血液或呼吸道样本中）；和 (iii) 识别预先选择的通用表位的抗体。通过这项工作，我们将为 加快新型流感疫苗研发。 分阶段的 UH2/UH3 计划将包括以下主要组成部分。 UH2可行性/早期 开发阶段我们将开发和优化测量抗体所需的检测试剂 对 10 种最近的疫苗毒株以及几种历史人类毒株和潜在大流行的反应 禽类。在此阶段，我们还将优化检测格式并组装样本集以供后续验证 工作。在 UH3 验证阶段，我们将建立生产检测试剂盒的制造程序，以 进行所提出的测定方法，并通过测试充分表征的样本集来验证性能 将我们的结果与既定的黄金标准方法进行比较。 †本提案中标有星号的文档部分包含 MSD 要求不得公开的专有/机密信息 政府以外的人员，但出于审查和评估目的的人员除外。