Research to Control and Eliminate Malaria in SE Asia and SW Pacific AI089686 Comp

描述（由申请人提供）：生活在恶性疟原虫（Pf）和间日疟原虫（Pv）流行地区的人们在童年和青春期反复接触寄生虫后，会自然获得对疟疾血期感染和疾病的免疫力。由于各地在传播强度和时间稳定性方面的差异，这种免疫力的发展速度是可变的。目前正在进行一项全球努力，通过使用驱虫蚊帐等病媒干预措施，控制并最终消除蛲虫病和蛲虫病。这里提出的研究目标是确定新的和强大的抗体检测来指导这一努力。用含有2320种Pf蛋白的蛋白质芯片检测暴露于Pf的马里儿童和成人的血清，结果表明，在多年反复感染Pf后，可获得针对数百种抗原的长期抗体反应，并鉴定出针对49种特异性Pf抗原的相关抗体。在这里，我们的目标是通过全球血清流行病学分析来扩展这些发现。这一多重icemr项目将在世界各地疟疾传播强度和疟原虫种类暴露程度不同的5个区域进行横断面和纵向研究，对样本进行探测。该阵列将包含来自Pf和Pv的800种抗原，每年将检测来自这些研究的血清，以确定媒介控制和化学预防对血清学反应的发展和下降的影响。这项研究将使我们更好地理解自然获得性免疫是如何随着年龄和季节性蚊子暴露而发展的。这些数据还可能导致发现与寄生虫接触和疟疾防护相关的抗体生物标志物。

DESCRIPTION (provided by applicant): People living in areas where Plasmodium falciparum (Pf) and P. vivax (Pv) are endemic develop naturally acquired immunity to malaria blood stage infection and illness after repeated exposures to the parasite through childhood and adolescence. The rate at which this immunity develops is variable due to local differences in the intensity and temporal stability of transmission. A global effort is now underway to control and ultimately eliminate Pf and Pv through the use of vector interventions such as insecticidal bed nets. The goal of research proposed here is to identify novel and robust antibody assays to guide this effort. Probing a protein microarray containing 2,320 Pf proteins with sera collected from Pf-exposed Malian children and adults indicated that long-lived antibody responses against hundreds of antigens are acquired after years of repeated Pf infections and antibodies associated with protection were identified against 49 specific Pf antigens. Here we aim to extend these findings with a worldwide sero-epidemiological analysis. This multi-ICEMR project will probe specimens from cross sectional and longitudinal studies in 5 regions around the world which differ in malaria transmission intensity and in Plasmodium species exposure. The array will contain 800 antigens from Pf and Pv, and sera from the studies will be probed annually to determine the effect of vector control and chemoprevention on the development and decline of the serological response. This study will better our understanding of how naturally acquired immunity develops as a function of age and seasonal mosquito exposure. The data may also lead to the discovery of antibody biomarkers associated with parasite exposure and with protection from malarial disease.