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：
10084803
负责人：
Frances Eun-Hyung Lee
金额：
$ 63.16万
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/10084803
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.

人类疫苗耐用性，使用综合生物信息学和一种新颖的体外骨髓模仿。抽象的：长寿命的浆细胞（LLPC）一生维持保护性抗体的产生，是细胞的基础疫苗耐用性，需要骨髓（BM）微米以维持生存。在我们的实验室中，我们有将长寿命的病毒血清抗体与健康人的BM细胞室联系起来 BM（CD19-CD38HICD138+）PC子集，从而建立LLPC室。我们也发展了模仿BM微环境以维持PC存活的体外BM微小培养物。在此应用程序中，我们计划（1）使用这种新颖的体外BM模拟物开发疫苗耐用性的新型体外生物标志物与短暂的疫苗，急性病毒感染的早期血液ASC的机制相比疫苗，（2）识别疫苗接种后早期血液中LLPC前体的独特身份，以及（3）到 LLPC产生的研究机制在全身性红斑红血病模型中以高寿命抗体和丰富的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。