ACQUISITION OF IMMUNITY TO MALARIA IN CHILDREN AND ADULTS

儿童和成人获得疟疾免疫力

• 批准号: 6099798
• 负责人: ISABELLA A QUAKYI
• 金额: $ 10.77万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099798
• 关键词: Africa; Plasmodium falciparum; T lymphocyte; age difference; antigen presentation; antimicroorganism antibody; child (0-11); enzyme linked immunosorbent assay; genetic polymorphism; hemoglobin Ss; histocompatibility typing; immunity; immunogenetics; immunoprecipitation; longitudinal human study; lymphocyte proliferation; malaria; malaria vaccines; protozoal antigen; restriction fragment length polymorphism; western blottings; young adult human (21-34)

Malaria has become a major threat to children, pregnant women and the aging in Cameroon due to single and multiple drug resistance in Plasmodium falciparum malaria. New drugs, vector control measures and a malaria vaccine are a necessity. The need to characterize and understand the components of acquired immunity to malaria are urgent if we are to develop; a successful malaria vaccine that can be used in malaria endemic areas. Natural immunity to malaria does occur, albeit slowly, taking many years, and even then may not be complete. The slow development of immunity may be due to the differential and age-related responses to immunodominant, variant and conserved, subdominant P. falciparum immunologically relevant proteins. We and others have demonstrated that humoral and cellular responses to MSP-1, MSP-2, AMA-1, may be important for the induction of protective immunity. We hypothesize that children respond predominantly to immunodominant variant epitopes, leading to incomplete immunity, and older children and adults respond to conserved epitopes resulting in long term protective immunity. To test our hypotheses, we will examine over five years the cellular and humoral immune responses to these antigens in a rural study population including, infants ages 1-5 years, children in age groups of 6-10 and 10- 15 years, and adults aged 16-45 who are naturally exposed to malaria. We will also examine cellular immune responses to both conserved and variant epitopes from MSP-1, MSA-2, AND AMA-1 candidate vaccine antigens. The immune responses will be correlated with HLA type to determine whether HLA effects the specificity and/or rate of development of protective immunity. This study will be carried out through a unique partnership between researchers in the laboratory and in the field. Data provided on the immune status of the population may help identify those effector mechanisms required for protective immunity. Also, data from this study may help in the development of intervention strategies that will contribute to the control of malaria in Cameroon.

疟疾已成为对儿童、孕妇和 年喀麦隆单一和多重耐药导致的老龄化 恶性疟原虫疟疾。新药、病媒控制措施和 疟疾疫苗是必要的。有必要描述和描述 了解疟疾获得性免疫的组成部分在以下情况下是迫切的 我们将开发一种成功的疟疾疫苗，可用于 疟疾流行地区。对疟疾的自然免疫力确实存在，尽管 慢慢地，花了很多年，即使到那时也可能不完整。慢的 免疫的发展可能是由于差异和年龄相关的 对免疫显性、变异型和保守型、亚显性P. 恶性疟原虫免疫相关蛋白。我们和其他人有 证明对MSP-1，MSP-2，AMA-1， 可能对诱导保护性免疫很重要。我们 假设儿童主要对免疫显性变异体有反应 表位，导致不完全免疫，以及年龄较大的儿童和成年人 对保守的表位作出反应，从而产生长期保护性免疫。 为了测试我们的假设，我们将在五年内检查细胞和 农村研究人群对这些抗原的体液免疫应答 包括1-5岁的婴儿、6-10岁和10-10岁的儿童 15岁，以及16-45岁自然暴露于疟疾的成年人。 我们还将研究细胞免疫反应，包括保守的和 MSP-1、MSA-2和AMA-1候选疫苗抗原的变异表位。 免疫反应将与人类白细胞抗原分型相关联，以确定 人类白细胞抗原是否影响人类免疫缺陷病毒的特异性和/或发展速度 保护豁免权。这项研究将通过一项独特的 实验室和现场研究人员之间的伙伴关系。数据 提供关于人群免疫状况的信息可能有助于识别 保护性免疫所需的效应器机制。此外，数据来自 这项研究可能有助于制定干预策略， 将有助于喀麦隆控制疟疾。