Immune Signatures Associated with Plasmodium falciparum Control Following Natural

疟疾在世界范围内的负担是沉重的。感染恶性疟原虫 物种具有最具破坏性的影响，每年导致近100万非洲儿童死亡。 即便如此，基于两条证据，疟疾控制仍是一个现实的目标：1)反复接触这种寄生虫的人会随着年龄的增长产生自然免疫；2)红系前疫苗候选疫苗可以降低临床疾病的发病率。目前，实现这一目标的一个主要障碍是缺乏对疟疾免疫保护机制的深入了解，以指导合理的疫苗设计。 在这个项目中，我们提出了两个具体目标，这两个目标将使用全面的系统生物学方法，通过调查生活在疟疾流行地区的非洲人口的自然获得性免疫和疫苗诱导保护，来扩大疟疾的免疫学知识库。在目标1中，我们将确定与控制乌干达儿童和成人的寄生虫血症和获得性免疫有关的独特免疫特征。在目标2中，我们将与研究人员合作进行第三阶段RTS，S/AS01E疫苗许可试验，以确定幼儿疫苗保护的免疫原性和相关性。 作为这一令人兴奋的研究领域的相对较新的研究者，我们将贡献我们的集体专业知识 在与先进的系统生物学、生物信息学和网络分析相结合的大规模国际疫苗研究中，设计和进行全面的免疫学研究。我们在疟疾领域具有公认领导地位的西雅图同事将指导我们的努力，我们可以有效地利用这两个互动项目的成果。我们预计这些研究将为控制疟疾感染的先天和获得性免疫机制提供重要的洞察力。

The worldwide burden of malaria disease is profound. Infection with the Plasmodium falciparum species has the most devastating effect, causing the death of nearly one million African children each year. Even so, malaria control is a realistic goal, based on two lines of evidence: 1) natural immunity emerges with age in persons repeatedly exposed to the parasite; and 2) pre-erythrocytic vaccine candidates can reduce incidence of clinical disease. Currently, a major hindrance in achieving this goal is the lack of a deep understanding of the mechanisms of immune protection against malaria that can guide rational vaccine design. In this project we propose two Specific Aims that will use a comprehensive systems biology approach to broaden the immunologic knowledge base of malaria by investigating naturally acquired immunity and vaccine-induced protection in African populations living in malaria-endemic areas. In Aim 1, we will determine the distinct immune signatures associated with control of parasitemia and acquired immunity in Ugandan children and adults. In Aim 2, we will partner with investigators in the conduct of a phase III RTS,S/AS01E vaccine licensure trial to define the immunogenicity and correlates of vaccine protection in young children. As relatively new investigators in this exciting research field, we will contribute our collective expertise in the design and conduct of comprehensive immunologic studies in large-scale international vaccine studies in concert with advanced systems biology, bioinformatics and network analyses. Our Seattle colleagues with recognized leadership in the malaria field will guide our efforts, and we can efficiently build upon findings in the two interactive projects. We envision these investigations will lend significant insight into the innate and adaptive immune mechanisms that control malaria infection.