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.

我们的目的是开发更好的测定，以测量影响力后的人产生的抗体 或疫苗接种。我们将开发测定总抗体反应的测定法，并特别是 测量负责保护感染的抗体。通过使用高通量多路复用格式 采用可以准备和存储大量的试剂，这些测定将解决许多实际的 当前金标准方法的局限 中和（MN）测定。这些测定将使用Meso ScaleDiagnostics®（MSD）电化学发光 （ECL）测定平台，该平台已被广泛用于Covid-19，肺炎球菌和其他的资格 疫苗。这些测定将使用带有阵列的多孔板，每个井中都有影响 支持对真空中代表的应变的抗体的简单测量，并 分析针对其他感兴趣菌株的交叉保护。一组检测试剂和测定格式将是 开发了该抗原阵列组件时，将支持一系列测量方式。 这些包括（i）抗体的测量，这些抗体阻断了每种抗原识别唾液酸的能力 （SA）修饰的宿主蛋白； （ii）针对每种抗原的总IgG和/或IgA（在血液或呼吸样本中）；和 （iii）识别预选的通用表位的抗体。通过这项工作，我们将为 加速新影响疫苗的发展。 分阶段的UH2/UH3程序将包括以下主要组件。在UH2可行性/早期 开发阶段我们将开发并优化测量抗体所需的必需测定试剂 对最近10种疫苗菌株以及几种历史人物菌株和潜在大流行的反应 禽流量。在此阶段，我们还将优化测定格式和组装样品集以供以后验证 工作。在UH3验证阶段，我们将建立生产测定套件的制造程序 进行拟议的测定方法，并通过测试特征良好的样品集验证性能和 将我们的结果与已建立的黄金标准方法进行比较。 †本提案中包含的文档部分标记了星号，包含专有/机密信息，MSD请求未发布到 除了审查和评估目的外，政府以外的人。