Assessing Flu-specific Humoral Immunity in Human Lung after Ex Vivo Lung Perfusion

评估离体肺灌注后人肺的流感特异性体液免疫

• 批准号: 10088408
• 负责人: Anoma Nellore
• 金额: $ 22.28万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10088408
• 关键词: Address; Adenovirus Vector; Affinity; Antibody Formation; Antigens; Arteries; Attenuated; Avidity; B-Cell Antigen Receptor; Binding; Biological Assay; Biological Models; Biopsy; Blood; Brain; Brain Death; Bronchoscopy; Cardiopulmonary; Cell surface; Cells; Clinical; Data; Dose; Epitopes; Family suidae; Formulation; Future; Gases; Generations; Goals; Harvest; Head; Hemagglutinin; Hour; Human; Humoral Immunities; Immune; Immune response; Immunity; Immunoglobulin Somatic Hypermutation; Immunoglobulin-Secreting Cells; In Situ; Infection; Influenza; Kinetics; Knowledge; Left atrial structure; Lung; Lung diseases; Lymph Node Tissue; Lymphoid; Lymphoid Tissue; Mediastinal lymph node group; Membrane; Memory; Memory B-Lymphocyte; Modality; Modeling; Mucous Membrane; Mus; Mutation; Organ; Organ Donor; Perfusion; Phenotype; Recombinant Antibody; Regimen; Research; Respiratory System; Structure of germinal center of lymph node; Structure of parenchyma of lung; Support System; Testing; Time; Tissue Viability; Tissues; Transgenes; Transplantation; Vaccine Design; Vaccines; Variant; Viral; Virus; cell type; chemokine; cost; design; flu; immunogenic; immunoregulation; influenza infection; influenza virus strain; influenzavirus; innovation; lymphoid organ; pandemic disease; pandemic influenza; post-transplant; response; seasonal influenza; universal influenza vaccine; universal vaccine; ventilation

PROJECT SUMMARY. Broadly reactive humoral immune responses to flu protect against viral variants. Murine data shows that the flu-specific memory B cells (Bmem) in the lung are cross-protective across a number of influenza strains and are functionally distinct from circulating and lymphoid counterparts. As yet we do not know if flu-specific Bmem in the human lung are cross-protective and bridging this knowledge gap is important to design the appropriate vaccine regimens that are universally protective against flu. Flu-specific Bmem in ex vivo lung tissues are rare and this represents a significant technical hurdle in assaying the flu-specific Bmem response in human lung tissues. In order to address this technical hurdle, this application seeks to establish a model system wherein human lung tissue is challenged with influenza virus and maintained viable after this challenge on an advanced cardiopulmonary modality called Ex Vivo Lung Perfusion or EVLP. We anticipate this model will allow us to enumerate and analyze the flu-specific Bmem response at scale in ex vivo human lung tissues. We also anticipate that this model system will allow us to compare binding reactivity to viral variants between flu- specific Bmem located in lung versus mediastinal lymph node tissues to define where cross-protective immunity exists in the respiratory tract.

项目摘要。对流感病毒的广泛反应性体液免疫反应可以保护人体免受病毒变异的侵害。鼠 数据显示，肺中的流感特异性记忆B细胞（BCLs）在许多疾病中具有交叉保护作用。 流感病毒株，并且在功能上不同于循环和淋巴对应物。我们还不知道 如果人肺中的流感特异性β-内酰胺酶具有交叉保护作用， 设计适当的疫苗方案，普遍预防流感。离体流感特异性生物素 肺组织是罕见的，这代表了在测定流感特异性的贝氏反应中的一个重要技术障碍 在人类肺组织中。为了解决这一技术障碍，本申请寻求建立一种模型， 其中人肺组织用流感病毒攻击并在该攻击后保持存活的系统 一种先进的心肺模式，称为体外肺灌注或EVLP。我们预计这一模式将 使我们能够在离体人肺组织中大规模地计数和分析流感特异性的BELF应答。我们 我还预计，这个模型系统将使我们能够比较流感病毒之间的病毒变体的结合反应性， 位于肺与纵隔淋巴结组织中的特异性抗体，以确定交叉保护性免疫的位置 存在于呼吸道中。