Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort.
Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort.
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DOI：
10.1128/cvi.00452-15
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发表时间：
2016-02
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影响因子：
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通讯作者：
Kazura JW
中科院分区：
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作者：
Dent AE;Malhotra I;Wang X;Babineau D;Yeo KT;Anderson T;Kimmel RJ;Angov E;Lanar DE;Narum D;Dutta S;Richards J;Beeson JG;Crabb BS;Cowman AF;Horii T;Muchiri E;Mungai PL;King CL;Kazura JW
抗恶性疟原虫IgG抗体在妊娠期间从母体循环转移到胎儿循环，出生后减弱，随后在自然感染时获得。我们通过（i）血清学，（ii）变异表面抗原（VSA）测定，（iii）生长抑制活性（GIA）和（iv）裂殖子表面蛋白1（MSP 1）和唾液酸依赖性侵袭途径特异性侵袭抑制测定（IIA），研究了84名肯尼亚婴儿从出生到36个月龄的疟疾抗体应答动态。在脐带血中检测到这四种类型的母体抗体，并在大约6个月大时降至最低水平。随后，3个红细胞前抗原和10个血液阶段抗原的血清学抗体增加，在36个月时达到患病率高峰。相比之下，通过VSA、GIA和IIA测量的抗体甚至在36个月内仍然很低。胎儿在子宫内对恶性疟原虫致敏（定义为脐带血淋巴细胞对疟疾抗原的回忆反应）的婴儿获得抗疟抗体的速率与在子宫内未致敏的婴儿相同，表明胎儿暴露于疟疾抗原并不影响随后的婴儿抗疟反应。在12个月大时可检测到血清学抗体的婴儿在随后的24个月内感染恶性疟原虫的风险增加。我们的结论是，在36个月或更年轻的儿童抗疟抗体的血清学措施代表疟疾暴露的生物标志物，而不是保护和功能性抗体在36个月后的年龄在这个人群中发展。
IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero, defined by cord blood lymphocyte recall responses to malaria antigens, acquired antimalarial antibodies at the same rate as those who were not sensitized in utero, indicating that fetal exposure to malaria antigens did not affect subsequent infant antimalarial responses. Infants with detectable serologic antibodies at 12 months of age had an increased risk of P. falciparum infection during the subsequent 24 months. We conclude that serologic measures of antimalarial antibodies in children 36 months of age or younger represent biomarkers of malaria exposure rather than protection and that functional antibodies develop after 36 months of age in this population.