Immune Responses Associated with Malaria Infection and Immune Protection - Project 1

与疟疾感染和免疫保护相关的免疫反应 - 项目 1

• 批准号: 10198681
• 负责人: KENNETH D STUART
• 金额: $ 76.46万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-19 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198681
• 关键词: Affect; Antibodies; Antigens; Attenuated; B-Lymphocytes; Biological Assay; CD8B1 gene; Cells; Characteristics; Complex; Culicidae; Data Pooling; Development; Erythrocytes; Evolution; Future; Gene Expression Profile; Goals; Grant; Granzyme; HIV Infections; HIV immunization; Human; Immune; Immune response; Immune signaling; Immune system; Immunity; Immunization; Immunologics; Infection; Infection prevention; Interferon Type II; Intravenous; Kinetics; Lead; Liver; Malaria; Memory; Methods; MicroRNAs; Molecular; Outcome; Parasites; Plasmodium falciparum; Process; Production; Protocols documentation; Sampling; Serum; Signal Transduction; Sporozoites; Statistical Methods; Systems Biology; T-Lymphocyte; Testing; Vaccination; Vaccines; Variant; chemokine; cytokine; effector T cell; high dimensionality; in vitro Assay; insight; malaria infection; pathogen; primary endpoint; response; secondary endpoint; vaccine trial; vaccine-induced immunity; virtual

Scientific Project 1: Immune Responses to Preerythocytic Malaria This project will comprehensively define human immune responses during the pre-erythrocytic stage of Plasmodium falciparum infection and vaccination with attenuated sporozoites which prevents infection and thus target this stage. It will identify immune signatures during the pre-erythrocytic, immunization and post vaccination periods in complementary vaccine trials that assess protection by controlled human malaria infection (CHMI). The primary endpoint is a correlation of vaccine-induced protection from infection, secondary endpoints are the effects of prior malaria exposure and differences in immunization protocols, vaccines and CHMI methods. The exploratory endpoints include the identification of signals that implicate immune processes that contribute to protection. The approach combines formal statistical methods, well-defined endpoints and system biology analyses. It systematically integrates high-dimensional with diverse immunological analyses to generate an expansive immunological view to identify and assess signals that are associated with protection. It aims to: 1. Identify immune responses during the pre-erythrocytic stages of infection. Virtually nothing is known about this stage the infection in the liver during which there is extensive parasite replication and synthesis of new antigens. We will identify signals of infection and of immunization with attenuated SPZs during this stage and compare variations among trials. 2. Determine immune response kinetics over the immunization period. We will identify the kinetics of innate and adaptive immunological signals during immunization with attenuated SPZs and identify the development of those that correlate with protection and how these differ among the trials. We will deduce molecular and cellular features from the signals that correlate with each variable to provide insight into immune processes that are associated with each endpoint. 3. Compare responses at and following of malaria challenge infection. We will identify signatures in samples from vaccinees prior to and following assessment by CHMI of protection from infection. We will compare immune signatures that are associated with each endpoint. The results from all of the aims will be used to guide the selection and testing of specific hypotheses about the mechanisms that underlay each of the endpoints. Overall, the comprehensive and integrated immunological and systems biology analyses will identify immune signatures during the critical stage of infection by and immune protection against a complex protozoan pathogen. It will generate and analyze pooled data from multiple complementary vaccine trials in order to identify correlates of protection from infection, how these are affected by variables among the trials. It will provide insight into multiple aspects of immune processes that are operative during infection and affected by vaccination.

科学项目1：免疫反应对脑细胞疟疾的反应 该项目将全面定义人类免疫反应， 恶性疟原虫感染和疫苗接种孢子虫，可防止感染和 因此针对这个阶段。它将在预性，免疫和后期识别免疫特征 互补疫苗试验中的疫苗接种期，以评估受控人类疟疾的保护 感染（CHMI）。主要终点是疫苗诱导的免受感染的保护的相关性 终点是先前疟疾暴露的影响以及免疫方案，疫苗和 CHMI方法。探索性终点包括识别暗示免疫过程的信号 这有助于保护。该方法结合了形式的统计方法，定义明确的终点和 系统生物学分析。它系统地将高维度与各种免疫学分析相结合到 产生广泛的免疫学观点，以识别和评估与保护相关的信号。它 目的是：1。在感染前肉毒杆细胞阶段确定免疫反应。几乎什么都没有 关于此阶段的肝脏感染已知，在此期间，寄生虫复制和 新抗原的合成。我们将确定感染信号和衰减的SPZ的免疫信号 在此阶段，并比较试验之间的变化。 2。确定有关的免疫反应动力学 免疫期。我们将在期间确定先天和适应性免疫信号的动力学 通过衰减的SPZ进行免疫接种，并确定与保护和保护相关的人的发展 这些在试验中有何不同。我们将从相关的信号中推断出分子和细胞特征 每个变量都可以深入了解与每个端点相关的免疫过程。 3。 比较疟疾挑战感染的反应。我们将确定样品中的签名 从CHMI评估疫苗对感染的保护。我们将比较 与每个端点相关的免疫特征。所有目标的结果将用于 指导对每个基础的机制的特定假设的选择和测试 端点。总体而言，全面和综合的免疫学和系统生物学分析将确定 在感染的关键阶段通过免疫特征和免疫保护对复杂的原生动物 病原。它将生成和分析来自多个互补疫苗试验的汇总数据，以便 确定保护免受感染的相关性，这些相关性如何受到试验中变量的影响。会 提供有关免疫过程的多个方面的见解 疫苗接种。