Immunoglobulin G Subclass-Specific Responses against Plasmodium falciparum Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness
Immunoglobulin G Subclass-Specific Responses against Plasmodium falciparum Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness
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DOI：
10.1128/iai.01129-08
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发表时间：
2009-03-01
影响因子：
3.1
通讯作者：
Beeson, James G.
中科院分区：
文献类型：
--
作者：
stanisic, Danielle I.;Richards, Jack S.;Beeson, James G.
大量的证据表明，恶性疟原虫裂殖子抗原的抗体在保护免受疟疾中发挥作用，尽管介导免疫的精确靶点和机制仍不清楚。不同的疟疾抗原诱导不同的免疫球蛋白G（IgG）亚类反应，但不同的反应在疟疾保护性免疫中的重要性尚不清楚，体内亚类反应的决定因素知之甚少。我们在巴布亚新几内亚的一个纵向队列中检测了裂殖子抗原MSP 1 -19（裂殖子表面蛋白1的19 kDa C-末端区域）、MSP 2（裂殖子表面蛋白2）和AMA-1（顶端膜抗原1）对IgG和IgG亚类的反应，包括这些抗原的不同多态性变体。IgG 1和IgG 3是每种抗原抗体的主要亚类，所有抗体应答均随年龄和暴露量增加而增加，但无证据表明向一个亚类的极化增加。IgG亚类的配置文件略有不同的MSP 2的不同等位基因，但不为不同的变体AMA-1。无论抗原如何，个体似乎没有做出特定亚类反应的倾向。相反，数据表明，对每种抗原的亚类反应是在个体之间独立产生的，并且抗原性质而不是宿主因素是IgG亚类反应的主要决定因素。高水平的AMA-1特异性IgG 3和MSP 1 -19特异性IgG 1强烈预测症状性疟疾和高密度恶性疟原虫感染的风险降低。然而，没有抗体应答与保护免受寄生本身显著相关。我们的发现对理解人类免疫力和疟疾疫苗的开发和评估具有重要意义。
Substantial evidence indicates that antibodies to Plasmodium falciparum merozoite antigens play a role in protection from malaria, although the precise targets and mechanisms mediating immunity remain unclear. Different malaria antigens induce distinct immunoglobulin G (IgG) subclass responses, but the importance of different responses in protective immunity from malaria is not known and the factors determining subclass responses in vivo are poorly understood. We examined IgG and IgG subclass responses to the merozoite antigens MSP1-19 (the 19-kDa C-terminal region of merozoite surface protein 1), MSP2 (merozoite surface protein 2), and AMA-1 (apical membrane antigen 1), including different polymorphic variants of these antigens, in a longitudinal cohort of children in Papua New Guinea. IgG1 and IgG3 were the predominant subclasses of antibodies to each antigen, and all antibody responses increased in association with age and exposure without evidence of increasing polarization toward one subclass. The profiles of IgG subclasses differed somewhat for different alleles of MSP2 but not for different variants of AMA-1. Individuals did not appear to have a propensity to make a specific subclass response irrespective of the antigen. Instead, data suggest that subclass responses to each antigen are generated independently among individuals and that antigen properties, rather than host factors, are the major determinants of IgG subclass responses. High levels of AMA-1-specific IgG3 and MSP1-19-specific IgG1 were strongly predictive of a reduced risk of symptomatic malaria and high-density P. falciparum infections. However, no antibody response was significantly associated with protection from parasitization per se. Our findings have major implications for understanding human immunity and for malaria vaccine development and evaluation.