ROLE OF DENDRITIC CELLS IN REGULATING VACCINE- INDUCED IMMUNITY AGAINST Q FEVER

树突状细胞在调节疫苗诱导的 Q 热免疫中的作用

• 批准号: 10049108
• 负责人: Guoquan Zhang
• 金额: $ 12.48万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10049108
• 关键词: Acute; Aerosols; Animals; Antigen-Presenting Cells; Bone Marrow; CD4 Positive T Lymphocytes; Cell Differentiation process; Cell Maintenance; Cell Maturation; Cells; Cellular Immunity; Chronic; Chronic Disease; Coculture Techniques; Coxiella burnetii; Data; Dendritic Cells; Development; Disease; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Formalin; Frequencies; Generations; Goals; Gram-Negative Bacteria; Health; Human; Immune; Immune response; Immunity; Immunize; Individual; Infection; Interleukin-12; Lipopolysaccharides; MHC Class II Genes; Major Histocompatibility Complex; Measurable; Measures; Mediating; Mus; Organism; Outcomes Research; Pattern; Peptides; Phase; Play; Prevention; Production; Q Fever; Risk; Role; T cell differentiation; T cell response; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Transgenic Mice; Vaccination; Vaccine Production; Vaccines; Variant; Virulent; Zoonoses; cytokine; design; flu; in vivo; mouse model; novel; pathogenic microbe; side effect; vaccine-induced immunity

Abstract Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute and chronic Q fever in humans. There is an urgent need to create a safe and effective vaccine for prevention of human Q fever. However, the mechanisms of vaccine-induced immunity against C. burnetii natural infection remain unclear. The long-term goal of this project is to develop a safe and effective vaccine against Q fever. The objective of this application, which is a critical step towards this goal, is to understand the role of dendritic cells (DCs) in regulating vaccine-induced immunity against Q fever and identify which type of T cell response is more critical for vaccine-induced protective immunity. To achieve this objective, two specific aims were proposed to test the central hypothesis that C. burnetii phase I vaccine (PIV) and phase II vaccine (PIIV) differentially activate DCs, thereby promoting distinct T cell responses are responsible for the difference in their ability to confer protection. Aim 1 will determine the role of DCs in regulating vaccine-induced immunity against Q fever by examining i) if PIV and PIIV differentially activate DCs, thereby promoting distinct T cell differentiation patterns in a mouse model; and ii) if DCs play a role in vaccine-induced protection against C. burnetii aerosol infection in vivo. Aim 2 will determine the role of CD4+ T cell subsets in PIV-induced protective immunity against C. burnetii aerosol infection by using a mouse model to investigate i) if PIV- and PIIV-induced T cell responses are responsible for the difference in their ability to confer protection; and ii) which CD4+ subset T cell response is more critical for PIV-induced protection. As an outcome of this research, it will gain novel information for understanding the role of DCs in regulating T cell-mediated immunity and determining the role of T cell responses in vaccine-induced protective immunity against C. burnetii infection. This is expected to have significant positive effects on publich health, because it will provide critical information for developing a safe and effective vaccine against Q fever.

摘要 伯氏柯克斯体是一种专性细胞内革兰氏阴性细菌，可引起急性和慢性Q热。 人类。迫切需要创造一种安全有效的疫苗来预防人类Q热。 然而，疫苗诱导免疫抵抗伯氏梭菌自然感染的机制尚不清楚。 该项目的长期目标是开发一种安全有效的Q热疫苗。的目标是 这一应用是实现这一目标的关键一步，目的是了解树突状细胞(DC)在 调节疫苗诱导的免疫对抗Q热，并确定哪种类型的T细胞反应更关键 疫苗诱导的保护性免疫。为了实现这一目标，提出了两个具体目标来测试 中心假设伯氏弧菌I期疫苗(PIV)和II期疫苗(PIIV)具有不同的激活作用 DC，从而促进不同的T细胞反应是它们授予能力的差异的原因 保护。目的1确定树突状细胞在调节疫苗诱导的Q热免疫中的作用 检查一)PIV和PIIV是否以不同方式激活DC，从而促进不同的T细胞分化模式 在小鼠模型中；以及ii)树突状细胞是否在疫苗诱导的预防伯氏梭菌气溶胶感染中发挥作用 在活体内。目的2确定CD4+T细胞亚群在PIV诱导的保护性免疫中的作用。 用小鼠模型研究伯氏杆菌气溶胶感染：1)PIV和PIIV是否诱导T细胞反应 它们提供保护的能力的不同；以及ii)哪些CD4+T细胞亚群反应 对于PIV诱导的保护更为关键。作为这项研究的结果，它将获得新的信息 了解树突状细胞在调节T细胞免疫中的作用和确定T细胞的作用 疫苗诱导对伯氏梭菌感染的保护性免疫应答。预计这将会有 对公众健康的重大积极影响，因为它将为制定安全的 以及有效的Q热疫苗。