Centre for Medical Parasitology at the Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2012;7(9):e43663. doi: 10.1371/journal.pone.0043663. Epub 2012 Sep 6.
Malaria during pregnancy in Plasmodium falciparum endemic regions is a major cause of mortality and severe morbidity. VAR2CSA is the parasite ligand responsible for sequestration of Plasmodium falciparum infected erythrocytes to the receptor chondroitin sulfate A (CSA) in the placenta and is the leading candidate for a placental malaria vaccine. Antibodies induced in rats against the recombinant DBL4ε domain of VAR2CSA inhibit the binding of a number of laboratory and field parasite isolates to CSA. In this study, we used a DBL4ε peptide-array to identify epitopes targeted by DBL4ε-specific antibodies that inhibit CSA-binding of infected erythrocytes. We identified three regions of overlapping peptides which were highly antigenic. One peptide region distinguished itself particularly by showing a clear difference in the binding profile of highly parasite blocking IgG compared to the IgG with low capacity to inhibit parasite adhesion to CSA. This region was further characterized and together these results suggest that even though antibodies against the synthetic peptides which cover this region did not recognize native protein, the results using the mutant domain suggest that this linear epitope might be involved in the induction of inhibitory antibodies induced by the recombinant DBL4ε domain.
在恶性疟原虫流行地区，妊娠期间疟疾是导致孕产妇死亡和严重发病的主要原因。VAR2CSA 是寄生虫配体，负责将恶性疟原虫感染的红细胞附着于胎盘上的硫酸软骨素 A（CSA）受体，是一种胎盘疟疾疫苗的主要候选物。针对重组 VAR2CSA 的 DBL4ε 结构域的抗体在大鼠中诱导产生，可抑制许多实验室和现场寄生虫分离株与 CSA 的结合。在这项研究中，我们使用 DBL4ε 肽微阵列来鉴定针对 DBL4ε 特异性抗体的表位，这些抗体可抑制感染红细胞与 CSA 的结合。我们鉴定了三个重叠肽的区域，这些区域具有高度的抗原性。一个肽区域特别突出，其高寄生虫阻断 IgG 的结合谱与低能力抑制寄生虫与 CSA 附着的 IgG 相比有明显差异。该区域进一步进行了表征，这些结果表明，尽管针对覆盖该区域的合成肽的抗体不能识别天然蛋白，但使用突变结构域的结果表明，该线性表位可能参与了重组 DBL4ε 结构域诱导的抑制性抗体的产生。
