Memory T follicular helper cell kinetics and localization during recall immune responses to tetanus vaccination

记忆 T 滤泡辅助细胞动力学和破伤风疫苗接种免疫反应过程中的定位

• 批准号: 10455483
• 负责人: Anne Elizabeth Parker Frosch
• 金额: $ 19.56万
• 依托单位: HENNEPIN HEALTHCARE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-12 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455483
• 关键词: Achievement; Acute; African; Antibodies; Antibody Affinity; Antibody Response; Antigens; Biological Assay; Blood; CD4 Positive T Lymphocytes; Cell Count; Cell Cycle Kinetics; Cell physiology; Cells; Cellular biology; Characteristics; Data; Development; Disease; Dose; Effector Cell; Epidemic; Epitopes; Fine needle aspiration biopsy; Flow Cytometry; Foundations; Future; Generations; Goals; HIV; Haplotypes; Helper-Inducer T-Lymphocyte; Human; Immune; Immune response; Immune system; Immunity; Immunologics; Immunologist; Immunology; Infection; Infection prevention; Infrastructure; Kinetics; Knowledge; Lead; Listeria monocytogenes; Location; Lymph Node Mapping; Lymphocyte; Lymphoid Tissue; MHC Class II Genes; Malaria; Malaria Vaccines; Measurement; Measures; Medical; Memory; Methods; Mus; Outcomes Research; Peptides; Peripheral Blood Mononuclear Cell; Phase; Phenotype; Plasma; Population; Proteins; Protocols documentation; Reagent; Research; Resources; Sampling; Science; Secondary to; Sentinel Lymph Node; Series; Serum; Site; Spleen; Stains; Supporting Cell; T cell response; T memory cell; Techniques; Technology; Testing; Tetanus; Tetanus Toxoid; Tetanus Vaccine; Tissues; Travel; Tweens; Vaccination; Vaccine Antigen; Vaccine Design; Vaccine Research; Vaccines; Work; aluminum sulfate; base; booster vaccine; career; design; draining lymph node; experimental study; falls; human subject; human tissue; innovation; interest; lymph nodes; novel vaccines; response; skills; symposium; tool; tool development; vaccine candidate; vaccine response; vaccine trial; vaccine-induced antibodies; vaccine-induced immunity

Project Summary/Abstract T follicular helper cells (Tfh) are a type of immune system cell that provide critical support in the generation of antibodies during vaccination. Understanding the mechanism by which these cells support highly efficacious and durable vaccine responses could assist in the development of novel vaccines targeting diseases such as malaria. Most of our knowledge on the characteristics and function of Tfh has come from basic immunology research done in mice. To study Tfh responses in mice, the convention has been to sample specialized immune tissues such as lymph nodes and spleen. In humans, these tissues are not readily accessible for study, so human immunologists study blood Tfh responses. Unfortunately, blood Tfh are thought to travel to lymphoid tissue when their relevant antigen enters the body. Thus, study of Tfh responses in blood is unlikely to reveal the helper T cell functions during vaccination that lead to the antibodies that provide protective immunity. The proposed project aims to characterize the Tfh response in both blood and lymphoid tissue in mouse and human hosts in response to vaccination. The goal of this work will be to determine whether measuring blood Tfh can be reliably used to study lymph node Tfh responses in human studies. During this study we will develop and optimize highly innovative techniques including vaccine-specific Tfh cell tracking, combined with lymph node mapping and serial lymph node sampling. These techniques will be used to track vaccine specific Tfh responses at their primary site of action. This project will serve as the foundation for future Tfh studies of vaccines, providing key technologies for studying Tfh and knowledge about Tfh localization during a vaccine response. These tools and knowledge will then be used to study Tfh responses in malaria vaccines, which have low efficacy in field-based studies. The goal of these future studies will be to inform novel vaccine design and administration protocols in pursuit of a highly efficacious malaria vaccine.

项目总结/摘要 滤泡辅助性T细胞（Tfh）是一种免疫系统细胞，其在免疫细胞的产生中提供关键支持。 疫苗接种期间的抗体。了解这些细胞支持高效的 持久的疫苗反应可以帮助开发针对疾病的新型疫苗， 疟疾我们对转铁蛋白的特性和功能的认识大多来自基础免疫学 在老鼠身上进行的研究。为了研究小鼠中的Tfh反应，惯例是对小鼠进行专门的取样。 免疫组织如淋巴结和脾。在人类中，这些组织不容易接近， 因此，人类免疫学家研究血液Tfh反应。不幸的是，血液Tfh被认为是旅行到 当相关抗原进入体内时，淋巴组织会发生反应。因此，不太可能研究血液中的Tfh应答 揭示辅助性T细胞在疫苗接种过程中的功能，从而产生提供保护性的抗体。 免疫力拟议的项目旨在描述血液和淋巴组织中的Tfh反应， 小鼠和人类宿主对疫苗接种的反应。这项工作的目标将是确定是否 测量血液Tfh可以可靠地用于研究人类研究中的淋巴结Tfh应答。在此 我们将开发和优化高度创新的技术，包括疫苗特异性Tfh细胞跟踪， 结合淋巴结定位和连续淋巴结取样。这些技术将用于跟踪 疫苗特异性Tfh应答在其主要作用位点。该项目将作为未来的基础。 Tfh疫苗研究，提供研究Tfh的关键技术和Tfh定位的知识 在疫苗反应中。这些工具和知识将用于研究Tfh在疟疾中的反应 疫苗，在实地研究中效力较低。这些未来研究的目标将是告知小说 疫苗设计和给药方案，以寻求高效疟疾疫苗。