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: 10670817
• 负责人: Anne Elizabeth Parker Frosch
• 金额: $ 19.44万
• 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/10670817
• 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; 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; Vaccination; Vaccine Antigen; Vaccine Design; Vaccine Research; Vaccines; Work; aluminum sulfate; booster vaccine; career; design; draining lymph node; experimental study; falls; human subject; innovation; interest; lymph nodes; migration; 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.

项目概要/摘要 滤泡辅助 T 细胞 (Tfh) 是一种免疫系统细胞，为免疫细胞的生成提供关键支持 疫苗接种期间产生抗体。了解这些细胞支持高效的机制 持久的疫苗反应可以帮助开发针对以下疾病的新型疫苗： 疟疾。我们对Tfh特性和功能的大部分了解都来自基础免疫学 在小鼠身上进行的研究。为了研究小鼠的 Tfh 反应，惯例是取样专门的 免疫组织，如淋巴结和脾脏。在人类中，这些组织不容易被利用 研究，因此人类免疫学家研究血液 Tfh 反应。不幸的是，血液 Tfh 被认为会流向 当其相关抗原进入体内时，淋巴组织。因此，不太可能研究血液中的 Tfh 反应 揭示疫苗接种过程中辅助 T 细胞的功能，从而产生提供保护性的抗体 免疫。拟议项目旨在表征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。这项工作的目标是确定是否 测量血液 Tfh 可可靠地用于研究人体研究中淋巴结 Tfh 反应。在此期间 研究中我们将开发和优化高度创新的技术，包括疫苗特异性 Tfh 细胞追踪， 结合淋巴结定位和连续淋巴结取样。这些技术将用于跟踪 疫苗在其主要作用位点产生特异性 Tfh 反应。该项目将作为未来的基础 疫苗的Tfh研究，为研究Tfh提供关键技术和Tfh本土化知识 在疫苗反应期间。这些工具和知识将用于研究疟疾中的 Tfh 反应 疫苗，在实地研究中效果较低。这些未来研究的目标将是为新的研究提供信息 疫苗设计和管理方案，以寻求高效的疟疾疫苗。

项目成果

Delayed clinical presentation of Plasmodium falciparum malaria after leaving an endemic area: a tale of two patients.

离开流行区后恶性疟原虫疟疾的临床表现延迟：两名患者的故事。

• DOI: 10.1093/jtm/taaa092
• 发表时间: 2020
• 期刊: Journal of travel medicine
• 影响因子: 25.7
• 作者: Pennington,Kaylin;Ives,SamuelT;Frosch,AnneEP;Shaughnessy,MeganK
• 通讯作者: Shaughnessy,MeganK

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial.

• DOI: 10.1016/s0140-6736(22)00101-5
• 发表时间: 2022-02-05
• 期刊: Lancet (London, England)
• 作者: ITAC (INSIGHT 013) Study Group

Recommendations and Guidance for Steroid Injection Therapy and COVID-19 Vaccine Administration from the American Society of Pain and Neuroscience (ASPN).

• DOI: 10.2147/jpr.s302115
• 发表时间: 2021
• 期刊: Journal of pain research
• 影响因子: 2.7
• 作者: Chakravarthy K;Strand N;Frosch A;Sayed D;Narra LR;Chaturvedi R;Grewal PK;Pope J;Schatman ME;Deer T
• 通讯作者: Deer T

C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial.

• DOI: 10.1136/thoraxjnl-2022-218744
• 发表时间: 2023-06
• 期刊: Thorax
• 影响因子: 10

Barriers to malaria prevention among immigrant travelers in the United States who visit friends and relatives in sub-Saharan Africa: A cross-sectional, multi-setting survey of knowledge, attitudes, and practices.

美国移民旅行者在撒哈拉以南非洲探亲访友时预防疟疾的障碍：一项关于知识、态度和实践的横断面、多环境调查。

• DOI: 10.1371/journal.pone.0229565
• 发表时间: 2020
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Volkman,HannahR;Walz,EmilyJ;Wanduragala,Danushka;Schiffman,Elizabeth;Frosch,Anne;Alpern,JonathanD;Walker,PatriciaF;Angelo,KristinaM;Coyle,Christina;Mohamud,MimiA;Mwangi,Esther;Haizel-Cobbina,Joseline;Nchanji,Comfort;Johnson
• 通讯作者: Johnson