Single cell molecular analysis of influenza vaccine responses in elderly individuals

老年人流感疫苗反应的单细胞分子分析

基本信息

批准号：
10574601
负责人：
Spyros A Kalams
金额：
$ 47.49万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10574601
关键词：
Adjuvant Adult Age Age Years Aging Antibodies Antibody titer measurement Antigens B-Lymphocytes CD4 Positive T Lymphocytes Cell Separation Cells Cellular Immunology Cytomegalovirus Dose Elderly Follow-Up Studies Frequencies Future Genes Health Helper-Inducer T-Lymphocyte Hospitalization Immune Immune response Immunity Immunoglobulin-Secreting Cells Immunologic Factors Impairment Individual Influenza Influenza vaccination Licensing MF59 Molecular Molecular Analysis Peripheral Plasma Cells Plasmablast Pneumonia Population Predictive Factor Reporting Seasons Series Structure of germinal center of lymph node T cell response T-Lymphocyte T-cell receptor repertoire Techniques United States Vaccination Vaccine Clinical Trial Vaccines alpha-beta T-Cell Receptor cohort design efficacy clinical trial human old age (65+)immune function improved individual response influenza virus vaccine lymph nodes pathogen prevent response senescence single cell sequencing transcriptomic profiling transcriptomics trial comparing vaccine response vaccine trial

项目摘要

PROJECT SUMMARY We will use cutting edge single T cell analysis techniques to molecularly define the T cell repertoire and function of cellular immune responses of individuals 65 years of age or older. The mechanisms behind declining immune responses with age is likely multifactorial. Aging is associated with a reduction in the frequency of antibody secreting cells and the number of lymph node germinal centers, and we hypothesize this to be due to impaired ability of CD4+ T cells to provide adequate help to B cells. T follicular helper cells in germinal centers directly provide help to B cells, and induce them to become antibody-secreting plasma cells. We have previously demonstrated the frequencies of activated peripheral T follicular helper cells (pTfh) and circulating plasmablasts shortly after vaccination is directly related to subsequent titers of vaccine-specific antibodies. Furthermore, high dose influenza vaccine (IIV HD) was better able to induce activated pTfh cells than standard dose vaccine (IIV SD). In this application we will probe the mechanisms behind successful immune responses to vaccines in an elderly population. We will evaluate the immune T cell repertoire, the transcriptomic profile of responding cells, and inflation of CMV-reactive T cells in elderly individuals and determine the effect of these factors on the host's ability to mount successful immune responses to vaccines. !

项目概要我们将使用尖端的单 T 细胞分析技术来从分子水平上定义 T 细胞库并 65 岁或以上个体的细胞免疫反应功能。背后的机制随着年龄的增长，免疫反应下降可能是多因素造成的。衰老与细胞减少有关抗体分泌细胞的频率和淋巴结生发中心的数量，我们假设这是由于 CD4+ T 细胞为 B 细胞提供足够帮助的能力受损。滤泡辅助T细胞生发中心直接为B细胞提供帮助，诱导其成为分泌抗体的血浆细胞。我们之前已经证明了外周滤泡辅助 T 细胞的激活频率 (pTfh) 和接种后不久的循环浆母细胞与随后的滴度直接相关疫苗特异性抗体。此外，高剂量流感疫苗（IIV HD）能够更好地诱导比标准剂量疫苗 (IIV SD) 更能激活 pTfh 细胞。在此应用中，我们将探讨其机制老年人群对疫苗产生成功免疫反应的背后。我们将评估免疫T 细胞库、响应细胞的转录组谱以及老年人 CMV 反应性 T 细胞的膨胀个体并确定这些因素对宿主成功免疫的能力的影响对疫苗的反应。！