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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的伯纳特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。迫切需要研制一种安全有效的疫苗来预防人类Q热。然而，疫苗诱导的针对伯氏念珠菌自然感染的免疫机制仍不清楚。该项目的长期目标是开发一种安全有效的 Q 热疫苗。的目标该应用是实现这一目标的关键一步，旨在了解树突状细胞 (DC) 在调节疫苗诱导的 Q 热免疫并确定哪种类型的 T 细胞反应更为关键用于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：伯内特衣原体 I 期疫苗 (PIV) 和 II 期疫苗 (PIIV) 的激活差异 DC 从而促进不同的 T 细胞反应，这导致了它们赋予能力的差异。保护。目标 1 将通过以下方式确定 DC 在调节疫苗诱导的 Q 热免疫中的作用：检查 i) PIV 和 PIIV 是否差异性激活 DC，从而促进不同的 T 细胞分化模式在小鼠模型中； ii) DC 是否在疫苗诱导的伯内特衣原体气溶胶感染保护中发挥作用体内。目标 2 将确定 CD4+ T 细胞亚群在 PIV 诱导的针对念珠菌的保护性免疫中的作用。使用小鼠模型研究伯内氏气溶胶感染 i) PIV 和 PIIV 是否诱导 T 细胞反应对他们提供保护的能力的差异负责； ii) 哪种 CD4+ 亚群 T 细胞反应对于 PIV 诱导的保护更为重要。作为这项研究的成果，它将获得新的信息了解 DC 在调节 T 细胞介导的免疫中的作用并确定 T 细胞的作用疫苗诱导的针对伯内特念珠菌感染的保护性免疫反应。预计这将有对公共卫生产生重大积极影响，因为它将为制定安全的方法提供关键信息以及针对 Q 热的有效疫苗。