Humoral responses to Plasmodium falciparum blood-stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa
Humoral responses to Plasmodium falciparum blood-stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa
复制标题
DOI：
10.1128/iai.01147-07
复制
发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Sirima, Sodiomon B.
中科院分区：
文献类型：
--
作者：
Nebie, Issa;Diarra, Amidou;Sirima, Sodiomon B.
长期以来有证据表明，免疫球蛋白G（IgG）在预防临床疟疾方面具有作用，而嗜细胞亚类的人抗体被认为在这方面特别重要。在这项队列研究中，对286名6个月至15岁的布基纳法索儿童进行疟疾监测，以评估针对四种抗原的抗体应答的保护作用，这些抗原目前正在评估为候选疫苗：顶端膜抗原1（AMA 1），裂殖子表面蛋白1-19（MSP 1 -19），MSP 3和富含谷氨酸的蛋白（GLURP）。总IgG，IgM和IgG亚类反应的疟疾传播季节之前进行了测量。疟疾发病率为每儿童危险年2.4次。校正年龄的混杂效应后，GLURP的总IgG水平与疟疾发病率降低密切相关（与总IgG加倍相关的发病率比为0.79; 95%置信区间为0.66 ~ 0.94; P = 0.009）;在针对MSP 3的总IgG水平和疟疾发病率之间存在临界统计学显著相关性，并且没有证据表明总IgG与AMA 1和MSP 1 -19相关。在所研究的IgG亚类应答中，仅抗GLURP的IgG 3和IgG 4以及抗AMA 1的IgG 1与临床疟疾风险降低相关。没有证据表明对AMA 1的反应和基线寄生虫血症对疟疾发病率的影响之间存在相互作用。这些血液阶段抗原AMA 1和GLURP目前包括在用于人类临床试验的疟疾疫苗制剂中，为疟疾疫苗开发提供了良好的前景。
There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabe children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P = 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development.