Suspension Array Technology for Malaria Abs in Neonates

新生儿疟疾抗体悬浮阵列技术

• 批准号: 6661982
• 负责人: ARMEAD H JOHNSON
• 金额: $ 23.28万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6661982
• 关键词: Plasmodium falciparum; antibody; antigen antibody reaction; clinical research; enzyme linked immunosorbent assay; human subject; humoral immunity; immunologic assay /test; malaria; measurement; newborn human (0-6 weeks); serum; suspensions; technology /technique development

DESCRIPTION (provided by applicant): Malaria caused by Plasmodium falciparum is a major public health problem. Millions die each year, mostly children and pregnant women. Infants, after losing the protection provided by passively acquired maternal Abs become susceptible to infection and disease. In endemic areas, infants become infected sometime in the 1st year and begin to develop their own immunity. Thus, longitudinal studies in infants provide an opportunity to assess the importance of Abs to specific malarial Ags as the infants rapidly change from resistant to susceptible to developing immunity. Little is known about this process. As only small amounts of blood can be repeatedly collected from infants, it has been impossible to study responses to multiple Ags. The innovative flow-based suspension array technology (SAT) provides an approach to do these studies. SAT is a quantitative indirect immunoassay that allows simultaneous measurement of Abs to multiple Ags, each coated to fluorospheres of different intensities. The overall aim of our parent grant is to identify tests that correlate with protective immunity to P. falciparum disease. Using ELISA, Abs to only two malarial Ags can be measured since only small amounts of blood can be collected. While the two Ags selected are important, Abs to Ags other than those being studied are implicated in protection to P. falciparum disease. Accordingly, the aim of this proposal is to develop and validate a test for measuring Abs to a panel of malarial Ags using the innovative SAT approach and to use this malarial Ag array to test the following hypotheses: 1) Infants who have high levels of maternal Abs at delivery to one or more of the Ags being tested will develop their first clinical episode later in life than infants born with low/no Abs to these Ags. 2) Infants who, following infection, produce Abs to one or more of the Ags being tested will have fewer malaria episodes between 6-12 months than infants who do not. Analysis of Abs to a panel of candidate Ags will provide greater potential to identify "correlates" of protection compared with our original proposal. In addition, validation of a SAT assay using a panel of functionally relevant malarial Ags would provide an important tool for the malaria research and vaccine development fields as well as expand the scope and potential of our parent study.

描述（由申请人提供）：恶性疟原虫引起的疟疾是一个主要的公共卫生问题。每年数以百万计的死亡，主要是儿童和孕妇。婴儿失去被动获得的母体ABS提供的保护后，婴儿容易受到感染和疾病的影响。在地方性地区，婴儿在第一年的某个时候被感染，并开始发展自己的免疫力。因此，随着婴儿从耐药性转变为敏感到发展免疫力，对婴儿的纵向研究提供了评估ABS对特定疟疾AG的重要性的机会。对这个过程知之甚少。由于只能从婴儿中反复收集少量血液，因此无法研究对多个AGS的反应。创新的基于流动的悬架阵列技术（SAT）提供了进行这些研究的方法。 SAT是一种定量的间接免疫测定法，可以同时对ABS同时测量多个AGS，每ABS都覆盖在不同强度的氟球体上。我们父母赠款的总体目的是确定与对恶性疟原虫疾病的保护性免疫相关的测试。使用ELISA，只能收集少量的血液，只能测量ABS至两个疟疾AG。虽然所选的两个AG很重要，但对被研究的AG的ABS涉及对恶性疟原虫疾病的保护。因此，该提案的目的是使用创新的SAT方法来开发和验证测试ABS向一组疟疾AG测量ABS，并使用该疟疾AG阵列来测试以下假设：1）在测试AGS中，在分娩时具有高水平的母体ABS的婴儿将与ABS相比，与ABS相比，与这些ABS相比，与这些AB的生命相比，与这些ABS相比，与这些ABS相比，与这些ABS相比，与这些临床相比，与这些临床相比，与这些ABS相比，与这些ags相比，不得以这些ag的生命来为这些临床症。 2）感染后，对一个或多个正在测试的AG产生ABS的婴儿的疟疾发作在6-12个月之间的疟疾发作少于没有的疟疾发作。与我们的原始提案相比，对ABS分析对候选AGS的分析将提供更大的潜力来识别保护的“相关”。此外，使用一组功能相关的疟疾AG对SAT测定的验证将为疟疾研究和疫苗发育领域提供重要的工具，并扩大我们父母研究的范围和潜力。