Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria
Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria
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DOI：
10.1128/iai.01585-07
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发表时间：
2008-05-01
影响因子：
3.1
通讯作者：
Marsh, Kevin
中科院分区：
文献类型：
--
作者：
Osier, Faith H. A.;Fegan, Gregory;Marsh, Kevin
生活在疟疾流行地区的个人会反复接触许多不同的疟原虫抗原。关于自然获得性抗体介导的临床疟疾免疫力的研究主要集中在对个体抗原的反应的存在及其与发病率降低的关系上。我们假设抗体反应的广度（产生抗体的重要靶标的数量）和强度（随机血清样本中测量的抗体水平）是预防临床疟疾的重要预测因素。我们分析了肯尼亚儿童中自然获得的针对五种主要恶性疟原虫裂殖子期疫苗候选抗原和裂殖体提取物的抗体，这些儿童接受了为期 6 个月的无并发症性疟疾监测（n = 119）。顶膜抗原 1 (AMA1) 和裂殖子表面蛋白抗原（MSP-1 block 2、MSP-2 和 MSP-3）的血清抗体水平与患疟疾的概率呈负相关，但 MSP-1(19) 和红细胞结合抗原 (EBA-175) 的水平则不然。疟疾的风险也与抗体特异性广度的增加呈负相关，同时对五种或更多抗原具有高抗体水平的儿童中没有一个经历过临床发作（17/119；15%；P = 0.0006）。特定的抗体组合（AMA1、MSP-2 和 MSP-3）比其他抗体组合更能预测保护作用。结果在一项更大规模的独立病例对照研究中得到了验证，该研究的终点是疟疾严重到足以入院（n = 387）。这些发现表明，在自然暴露下，对疟疾的免疫力可能来自针对多个抗原靶标的高滴度抗体，并支持测试优化以诱导相似抗体谱的组合血期疫苗的想法。
Individuals living in areas where malaria is endemic are repeatedly exposed to many different malaria parasite antigens. Studies on naturally acquired antibody-mediated immunity to clinical malaria have largely focused on the presence of responses to individual antigens and their associations with decreased morbidity. We hypothesized that the breadth (number of important targets to which antibodies were made) and magnitude (antibody level measured in a random serum sample) of the antibody response were important predictors of protection from clinical malaria. We analyzed naturally acquired antibodies to five leading Plasmodium falciparum merozoite-stage vaccine candidate antigens, and schizont extract, in Kenyan children monitored for uncomplicated malaria for 6 months (n = 119). Serum antibody levels to apical membrane antigen 1 (AMA1) and merozoite surface protein antigens (MSP-1 block 2, MSP-2, and MSP-3) were inversely related to the probability of developing malaria, but levels to MSP-1(19) and erythrocyte binding antigen (EBA-175) were not. The risk of malaria was also inversely associated with increasing breadth of antibody specificities, with none of the children who simultaneously had high antibody levels to five or more antigens experiencing a clinical episode (17/119; 15%; P = 0.0006). Particular combinations of antibodies (AMA1, MSP-2, and MSP-3) were more strongly predictive of protection than others. The results were validated in a larger, separate case-control study whose end point was malaria severe enough to warrant hospital admission (n = 387). These findings suggest that under natural exposure, immunity to malaria may result from high titers antibodies to multiple antigenic targets and support the idea of testing combination blood-stage vaccines optimized to induce similar antibody profiles.