Systems Biology in Vaccination Post Autologous Hematopoietic Cell Transplant

自体造血细胞移植后疫苗接种中的系统生物学

• 批准号: 8307076
• 负责人: MIRIAM MERAD
• 金额: $ 28.1万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-05 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307076
• 关键词: Adjuvant; Age; Age-Years; Allogenic; Antibody Formation; Antigen-Presenting Cells; Antigens; Autologous; B-Lymphocytes; BLR1 gene; Biological Assay; Biological Markers; Blood; Bone Marrow Transplantation; CD4 Positive T Lymphocytes; Cell Count; Cell Transplantation; Cell Transplants; Cell physiology; Cells; Combined Vaccines; Competence; Data; Dendritic Cells; Development; Disease; Disease remission; Dose; Evolution; Frequencies; Future; Gene Expression; Generations; Goals; Helper-Inducer T-Lymphocyte; Hematopoietic; Human; Immune; Immune Cell Activation; Immune response; Immune system; Immunization; Immunocompromised Host; Immunologic Markers; Individual; Influenza; Influenza vaccination; Instruction; Kinetics; Literature; Measures; Morbidity - disease rate; Multiple Myeloma; Patients; Protocols documentation; Recruitment Activity; Regimen; SELL gene; ST14 gene; Signal Transduction; System; Systems Analysis; Systems Biology; T cell response; T-Lymphocyte; Testing; Time; Transplantation; Vaccination; Vaccines; base; design; healthy volunteer; improved; influenza virus vaccine; monocyte; mortality; novel; prevent; reconstitution; response; vaccination strategy; Adjuvant; Age; Age-Years; Allogenic; Antibody Formation; Antigen-Presenting Cells; Antigens; Autologous; B-Lymphocytes; BLR1 gene; Biological Assay; Biological Markers; Blood; Bone Marrow Transplantation; CD4 Positive T Lymphocytes; Cell Count; Cell Transplantation; Cell Transplants; Cell physiology; Cells; Combined Vaccines; Competence; Data; Dendritic Cells; Development; Disease; Disease remission; Dose; Evolution; Frequencies; Future; Gene Expression; Generations; Goals; Helper-Inducer T-Lymphocyte; Hematopoietic; Human; Immune; Immune Cell Activation; Immune response; Immune system; Immunization; Immunocompromised Host; Immunologic Markers; Individual; Influenza; Influenza vaccination; Instruction; Kinetics; Literature; Measures; Morbidity - disease rate; Multiple Myeloma; Patients; Protocols documentation; Recruitment Activity; Regimen; SELL gene; ST14 gene; Signal Transduction; System; Systems Analysis; Systems Biology; T cell response; T-Lymphocyte; Testing; Time; Transplantation; Vaccination; Vaccines; base; design; healthy volunteer; improved; influenza virus vaccine; monocyte; mortality; novel; prevent; reconstitution; response; vaccination strategy

Influenza causes significant morbidity and mortality in hematopoietic cell transplantation (HCT) recipients, who are immunocompromised. Vaccination is the most effective way of preventing influenza but is less effective in immunocompromised patients than in healthy individuals. Thus, there is a need to understand the mechanisms underlying poor vaccine responses as well as establish biomarkers of immune competence. We surmise that understanding the relationships between antigen presenting cells (including monocytes and DCs), influenza-specific CD4+ T cells and antibody responses elicited by vaccination may enable a more rational design of vaccination strategies and timing in this group of patients. All studies to date have shown diminished CD4+ T cell numbers and proliferative T cell responses even at 12 months post transplant. We will utilize a systems biology analysis to define the immune alteration underlying the diminished responses to influenza vaccines in this group of patients. This will form a ground for development of new immuneenhancing strategies. We will focus on systems biology analysis of three cellular compartments that are essential for the generation and the quality of antibody responses to vaccines - the inducers (dendritic cells/monocytes and their subsets); regulators (T follicular helper cells - Tfh), and effectors (B cells). To date, there are no studies describing a systematic and comprehensive analysis of the reconstitution of these three blood compartments in patients who have undergone autologous HCT. Moreover, Tfh immune reconstitution after transplant (allogeneic or autologous) has not been examined for the identification of these cells until very recently. The alteration(s) in either or all of these compartments will have an impact on the quality of flu vaccine responses after HCT. Thus, our study presents an opportunity to analyze, at a systems level, the responses to flu vaccine in patients who have undergone HCT. Three aims are proposed: AIM 1: To establish the cellular and transcriptional signatures of response to flu vaccination in patients who underwent autologous HCT and in age-matched healthy volunteers. AIM 2: To establish the kinetics of blood DC subsets, Tfh and B cell compartments reconstitution in patients who underwent autologous HCT. AIM 3: To establish the functional competence of blood DC subsets and Tfh cells in patients who underwent autologous HCT.

流感引起造血细胞移植（HCT）受体的显着发病率和死亡率， 免疫功能低下的人。疫苗接种是预防流感的最有效方法，但较少 对免疫功能低下的患者有效，而不是健康个体。因此，有必要了解 疫苗反应不良的机制以及建立免疫能力的生物标志物。 我们推测，了解抗原呈递细胞之间的关系（包括单核细胞和 DCS），流感特异性的CD4+ T细胞和疫苗接种引起的抗体反应可能会更多 这组患者的疫苗接种策略和时间的合理设计。迄今为止的所有研究都表明 移植后12个月，CD4+ T细胞数量减少和增殖T细胞反应。我们 将利用系统生物学分析来定义对反应减少的免疫改变 这组患者的流感疫苗。这将构成开发新免疫力的基础 策略。我们将重点介绍三个细胞室的系统生物学分析 对于疫苗的产生和抗体反应的质量 - 诱导剂（树突状） 细胞/单核细胞及其子集）；调节剂（T卵泡辅助细胞-TFH）和效应子（B细胞）。迄今为止， 没有研究描述这三个重建的系统和全面分析 患有自体HCT的患者的血室。此外，TFH免疫重建 在移植后（同种异体或自体），尚未检查这些细胞的鉴定，直到 最近。这些隔室中的任何一个或全部的变化都会影响流感的质量 HCT后的疫苗反应。因此，我们的研究提供了一个在系统层面分析的机会 患有HCT的患者对流感疫苗的反应。提出了三个目标： 目的1：建立对患者流感疫苗反应反应的细胞和转录特征 接受了自体HCT，并在年龄匹配的健康志愿者中接受了。 目的2：建立患者血液直流子集的动力学，TFH和B细胞室的重建 谁接受了自体HCT。 目标3：建立接受血液DC子集和TFH细胞的功能能力 自体HCT。