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 Coxiella burnetii是一种强制性细胞内革兰氏阴性细菌，会引起急性和慢性Q热。人类。迫切需要创建一种安全有效的疫苗来预防人类Q发烧。然而，疫苗诱导的抗牛梭菌自然感染的免疫力的机制尚不清楚。该项目的长期目标是开发针对Q发烧的安全有效疫苗。目的该应用是朝着这一目标迈出的关键一步，是了解树突状细胞（DC）在调节疫苗诱导的抗Q发烧的免疫力，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 C. burnetii I期疫苗（PIV）和II期疫苗（PIIV）差异激活的中心假设 DC，从而促进不同的T细胞响应是其授予能力差异的原因保护。 AIM 1将确定DC在调节疫苗诱导的免疫对Q发烧的免疫力中的作用检查i）如果PIV和PIIV差异激活DC，从而促进了不同的T细胞分化模式在鼠标模型中； ii）如果DCS在疫苗诱导的针对C. burnetii气溶胶感染中发挥作用体内。 AIM 2将确定CD4+ T细胞亚群在PIV诱导的针对C的保护性免疫中的作用。使用小鼠模型研究burnetii气溶胶感染i）如果PIIV和PIIV诱导的T细胞反应负责他们提供保护能力的差异； ii）哪个CD4+子集T细胞响应对于PIV引起的保护更为重要。作为这项研究的结果，它将获得新的信息了解DC在调节T细胞介导的免疫和确定T细胞的作用中的作用疫苗诱导的保护性免疫的反应针对伯内特梭菌感染。这有望有对Publich Health的重大积极影响，因为它将为开发安全的关键信息提供关键信息和有效的疫苗抗Q热。