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Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic

使用综合生物信息学和新型体外骨髓模拟物研究人类疫苗的耐久性

基本信息

批准号：
10320908
负责人：
Frances Eun-Hyung Lee
金额：
$ 62.18万
依托单位：
EMORY UNIVERSITY
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：
2019-01-21 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10320908
关键词：
ATAC-seq Acute Affinity Antibodies Antibody Formation Antibody Repertoire Aspirate substance Autoantibodies Autoimmune Diseases B-Cell Antigen Receptor B-Lymphocytes Behavior Bioinformatics Biological Markers Blood Blood Circulation Bone Marrow CD19 gene Cell Compartmentation Cell Differentiation process Cell Maturation Cell Survival Cells Cellular Morphology Disease model Elderly Epigenetic Process Flow Cytometry Generations Genetic Transcription Hepatitis B Heterogeneity Homing Human Hypoxia Immune Immunization Immunoglobulin-Secreting Cells In Vitro Infection Interferon Type II Interleukin-6 Kinetics Life Link Lupus Maintenance Measles Mediating Methods Molecular Mumps Pathway interactions Patients Peripheral Plasma Cells Population Production Property Reaction Rubella Serum Smallpox Streptococcus pneumoniae Structure of germinal center of lymph node Survivors Systemic Lupus Erythematosus T-Lymphocyte Tetanus Time Vaccination Vaccines Viral Virus Diseases Yellow Fever Vaccine cytokine epigenome human disease imprint influenza infection influenza virus vaccine insight lymph nodes mesenchymal stromal cell next generation sequencing novel novel marker pandemic influenza programs reconstruction response transcriptome transcriptome sequencing transcriptomics vaccine evaluation vaccine response

项目摘要

Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic. Abstract: Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime and are the cellular basis of vaccine durability and require the bone marrow (BM) microniche to sustain survival. In our lab, we have definitively linked the long-lived viral serum antibodies to the BM cellular compartment within the healthy human BM (CD19-CD38hiCD138+) PC subset thereby establishing the LLPC compartment. We have also developed in vitro BM microniche cultures that mimic the BM microenvironment to sustain PC survival. In this application, we plan (1) to develop a novel in vitro biomarker of vaccine durability using this novel in vitro BM mimic and to dissect the mechanisms of early blood ASC of long-lived vaccines, acute viral infections, compared to short-lived vaccines, (2) to identify the unique identity of LLPC precursors in the blood early after vaccination, and (3) to study mechanisms of LLPC generation in disease models of Systemic Lupus Erythematosis which is characterized by high levels of long-lived antibodies and an abundance of LLPC. In summary, these studies will distinguish the cellular and molecular programs of LLPC generation and maintenance after immunization.

基于集成生物信息学和一种新型体外骨髓模拟物的人疫苗耐受性研究。摘要：长寿命浆细胞(LLPC)终生维持保护性抗体的产生，是疫苗的耐久性和需要骨髓(BM)微核率来维持生存。在我们的实验室里，我们有确定将长寿病毒血清抗体与健康人的骨髓细胞隔间联系起来 BM(CD19-CD38hiCD138+)PC亚集，从而建立LLPC亚群。我们还在模拟骨髓微环境的体外骨髓微培养，以维持PC的生存。在此应用程序中，我们计划(1)利用这种新型的体外BM模拟物开发一种新的疫苗耐受性的体外生物标志物，并剖析长效疫苗、急性病毒感染与短效疫苗早期血液ASC的机制疫苗，(2)在接种疫苗后早期确定血液中LLPC前体的独特身份，以及(3) 系统性红斑狼疮疾病模型LLPC生成机制的研究以高水平的长寿抗体和丰富的LLPC为特征。总而言之，这些研究将区分免疫后LLPC生成和维持的细胞和分子程序。