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：对前体细胞疟疾的免疫反应 该项目将全面定义红细胞前期的人类免疫反应， 恶性疟原虫感染和用减毒子孢子接种疫苗， 所以瞄准这个阶段。它将在红细胞前、免疫和免疫后识别免疫特征。 评估受控制的人类疟疾保护作用的补充疫苗试验中的疫苗接种期 感染（CHMI）。主要终点是疫苗诱导的感染保护，次要终点 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涉及免疫过程的信号 这有助于保护。该方法结合了正式的统计方法，定义明确的终点， 系统生物学分析它系统地整合了高维与各种免疫学分析， 生成一个扩展的免疫学视图，以识别和评估与保护相关的信号。它 目的是：1.确定感染红细胞前期的免疫反应。事实上， 已知这个阶段的感染在肝脏期间有广泛的寄生虫复制， 新抗原的合成。我们将确定感染和减毒SPZ免疫的信号 在这个阶段，并比较试验之间的变化。2.确定免疫应答动力学， 免疫期。我们将确定先天性和适应性免疫信号的动力学过程中， 用减毒SPZ免疫，并确定与保护相关的那些SPZ的发展， 这些在不同的试验中有何不同。我们将从相关的信号中推断出分子和细胞特征 与每个变量一起提供对与每个终点相关的免疫过程的洞察。3. 比较疟疾攻毒感染时和之后的反应。我们将在样本中识别签名 在CHMI评估预防感染之前和之后，从接种者中获得。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 指导选择和测试有关机制的具体假设， 端点。总的来说，全面和综合的免疫学和系统生物学分析将确定 在复杂原生动物感染的关键阶段的免疫特征和针对复杂原生动物的免疫保护 病原体它将生成和分析来自多个互补疫苗试验的汇总数据， 确定保护免受感染的相关性，以及这些相关性如何受到试验变量的影响。它将 深入了解在感染过程中起作用的免疫过程的多个方面， 预防针