ACQUISITION OF IMMUNITY TO MALARIA IN CHILDREN AND ADULTS

疟疾已成为儿童、孕妇和 由于单一和多重耐药性， 恶性疟原虫疟疾 新药物、病媒控制措施和 疟疾疫苗是必需的。 需要描述和 了解疟疾获得性免疫的组成部分是紧迫的， 我们将开发一种成功的疟疾疫苗， 疟疾流行区。 对疟疾的天然免疫确实存在，尽管 慢慢地，需要很多年，即使这样也可能不完整。 缓慢 免疫力的发展可能是由于不同的和年龄相关的 对免疫显性、变异和保守、亚显性P. 恶性疟原虫免疫相关蛋白。 我们和其他人已经 证明了对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作出反应 表位，导致不完全免疫，以及年龄较大的儿童和成人 对保守表位产生应答，从而产生长期保护性免疫。 为了验证我们的假设，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- 1-5岁的儿童， 15岁，16-45岁的成年人自然接触疟疾。 我们还将研究细胞免疫反应， 来自MSP-1、MSA-2和AMA-1候选疫苗抗原的变体表位。 将免疫应答与HLA类型相关联以确定 HLA是否影响特异性和/或发展速度， 保护性免疫 这项研究将通过一个独特的 实验室和实地研究人员之间的伙伴关系。 数据 提供的关于人群免疫状况的信息可能有助于识别那些 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， 将有助于喀麦隆的疟疾控制。

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.