Immune Profile and Network Analysis of Malaria Infection and Vaccination

描述（由申请人提供）：这是开发疟疾疫苗的合适时机(首次显示疫苗效力，并有望在正在进行的试验中获得非常有效的疫苗，计划在明年进行，并准备在资助期间进入1/2a期临床试验。来自强大机构并在疟疾、免疫学、系统生物学、疫苗和生物统计学方面具有互补专业知识的专家组成了一个联盟，利用现有的试验样本，详细描述抗疟疾免疫反应及其与免疫保护的关系。这一机会吸引了正在进行疫苗试验和将提供临床样本的人员的热情参与。这些试验的设计支持全面的免疫分析和网络分析评估。将从研究人群（包括未患疟疾的成人到生活在流行地区的儿童和成人）中，在接种疫苗和挑战或自然感染之前和之后获取样本。恶性疟原虫的范围从具有良好特征的临床分离株（例如NF54）到几个非洲国家的生物多样性自然种群。该项目将使用广泛的最佳方法来描述广泛的免疫反应和免疫细胞类型。这包括疟疾特异性白细胞表型、细胞因子和趋化因子谱、抗体反应以及转录和宿主DNA分析的多参数评估。这是为了生成免疫反应的概况，可以在系统生物学方法中与免疫状态和机制相关，并确定与免疫保护相关的功能网络。这项研究的目的是深入了解疟疾的保护性免疫机制，以便改进抗疟疾疫苗，并为总体上改进疫苗开发奠定基础，从而与社区共享。

DESCRIPTION (provided by applicant): It Is an opportune time for malaria vaccine (development with the first indication of vaccine efficacy and the promise of very effective vaccines in trials that are underway, planned for the coming year, and poised to enter phase 1/2a clinical trials during the grant period. A consortium of committed experts from strong institutions and with complementary expertise in malaria, immunology, systems biology, vaccines, and biostatistics has assembled to use the available trial samples in order to characterize in detail antimalarial immune responses and their relationship to immune protection. This opportunity attracted the enthusiastic participation of those who are conducting vaccine trials and who will provide the clinical samples. The design of these trials supports comprehensive immune profiling and network analysis assessment. Samples will be obtained prior to and following vaccination and challenge or natural infection from study populations that span malaria-naive adults to children and adults living in endemic regions. The P. falciparum parasites range from well characterized clinical isolates (e.g. NF54) to biodiverse natural populations in several African countries. The project will use a wide range of best-of-breed methodologies to characterize a wide range of immune responses and immune cell types. This includes multi-parametric assessments of malaria specific leukocyte phenotypes, cytokine and chemokine profiles, antibody responses, and transcriptional and host DNA analyses. This is designed to generate a profiles of immune responses that can in a systems biology approach be correlated with immune status and mechanisms and identify functional networks associated with immune protection. The study is designed to provide insight into protective immune mechanisms to malaria in order to improve anti-malarial vaccines and also to lay a foundation for improved vaccine development in general that can be shared with the community. RELEVANCE: A consortium of investigators with complementary expertise that span a wide range of high-end laboratory and informatic technologies have joined forces to comprehensively profile immune responses to malaria infection and the development of immunity. The overall goal of this project is to elucidate the mechanisms of immune protection to malaria in order to accelerate development of a broadly effective malaria vaccine and to advance the process of vaccine development in general.