Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawai'i-Mānoa, Honolulu, Hawaii, United States of America.
PLoS One. 2012;7(6):e40049. doi: 10.1371/journal.pone.0040049. Epub 2012 Jun 26.
VAR2CSA mediates sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, increasing the risk of poor pregnancy outcomes. Naturally acquired antibodies (Ab) to placental parasites at delivery have been associated with improved pregnancy outcomes, but Ab levels and how early in pregnancy Ab must be present in order to eliminate placental parasites before delivery remains unknown. Antibodies to individual Duffy-binding like domains of VAR2CSA have been studied, but the domains lack many of the conformational epitopes present in full-length VAR2CSA (FV2). Thus, the purpose of this study was to describe the acquisition of Ab to FV2 in women residing in high and low transmission areas and determine how Ab levels during pregnancy correlate with clearance of placental parasites. Plasma samples collected monthly throughout pregnancy from pregnant women living in high and low transmission areas in Cameroon were evaluated for Ab to FV2 and the proportion of high avidity Ab (i.e., Ab that remain bound in the presence of 3M NH(4)SCN) was assessed. Ab levels and proportion of high avidity Ab were compared between women with placental malaria (PM(+)) and those without (PM(-)) at delivery. Results showed that PM(-) women had significantly higher Ab levels (p = 0.0047) and proportion of high avidity Ab (p = 0.0009) than PM(+) women throughout pregnancy. Specifically, women with moderate to high Ab levels (>5,000 MFI) and those with ≥ 35% high avidity Ab at 5-6 months were found to have 2.3 (95% CI, 1.0-4.9) and 7.6-fold (p = 0.0013, 95% CI: 1.2-50.0) reduced risk of placental malaria, respectively. These data show that high levels of Ab to FV2, particularly those with high avidity for FV2, produced by mid-pregnancy are important in clearing parasites from the placenta. Both high Ab levels and proportion of high avidity Ab to FV2 may serve as correlates of protection for assessing immunity against placental malaria.
VAR2CSA 介导恶性疟原虫感染的红细胞在胎盘内的隐匿，增加了不良妊娠结局的风险。在分娩时自然获得的针对胎盘寄生虫的抗体（Ab）与改善妊娠结局相关，但 Ab 水平以及 Ab 必须在妊娠早期存在多长时间以在分娩前清除胎盘寄生虫仍然未知。已经研究了针对 VAR2CSA 类似 Duffy 结合结构域的单个抗体，但这些结构域缺乏全长 VAR2CSA（FV2）中存在的许多构象表位。因此，本研究的目的是描述在高传播和低传播地区居住的妇女对 FV2 的 Ab 获得情况，并确定妊娠期间 Ab 水平与清除胎盘寄生虫的相关性。评估了来自喀麦隆高传播和低传播地区的孕妇在整个妊娠期间每月收集的血浆样本中针对 FV2 的 Ab 以及高亲和力 Ab（即在存在 3M NH(4)SCN 时仍然结合的 Ab）的比例。比较了分娩时有胎盘疟疾（PM(+)）和无胎盘疟疾（PM(-)）的妇女之间的 Ab 水平和高亲和力 Ab 的比例。结果表明，整个妊娠期间 PM(-) 妇女的 Ab 水平（p = 0.0047）和高亲和力 Ab 的比例（p = 0.0009）明显高于 PM(+) 妇女。具体而言，在 5-6 个月时具有中等至高 Ab 水平（>5,000 MFI）和≥35%高亲和力 Ab 的妇女被发现分别具有 2.3（95%CI，1.0-4.9）和 7.6 倍（p = 0.0013，95%CI：1.2-50.0）降低患胎盘疟疾的风险。这些数据表明，妊娠中期产生的针对 FV2 的高水平 Ab，特别是针对 FV2 的高亲和力 Ab，对于清除胎盘内的寄生虫很重要。高 Ab 水平和针对 FV2 的高亲和力 Ab 的比例都可能成为评估针对胎盘疟疾的免疫保护的相关性。
