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

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.

流感在造血细胞移植（HCT）受者中引起显著的发病率和死亡率。