Differential recognition of P. falciparum VAR2CSA domains by naturally acquired antibodies in pregnant women from a malaria endemic area.
Differential recognition of P. falciparum VAR2CSA domains by naturally acquired antibodies in pregnant women from a malaria endemic area.
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DOI：
10.1371/journal.pone.0009230
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发表时间：
2010-02-16
期刊：
影响因子：
3.7
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Brolin KJ;Persson KE;Wahlgren M;Rogerson SJ;Chen Q
恶性疟原虫感染的红细胞（iRBC）表达变体表面抗原（VSA），其中VAR 2CSA参与胎盘隔离并引起妊娠相关疟疾（PAM）。Primigravidae是最容易受到PAM，而与保护相关的抗体往往存在于较高水平的多次妊娠妇女。然而，艾滋病毒与疟疾合并感染已被证明会改变这种依赖胎次获得免疫力的情况，艾滋病毒阳性妇女与同等胎次的艾滋病毒阴性妇女相比，症状更严重，疟疾发病率更高。使用CHO-745细胞表面上表达的VAR 2CSA DBL-结构域，我们通过流式细胞术定量来自马拉维孕妇的血清中DBL-结构域特异性IgG的水平。使用表面等离子体共振技术测定DBL 5 ε特异性抗体的解离常数，作为抗体亲和力的指示。VAR 2CSA DBL 5 ε以性别和胎次依赖性方式被识别，其中抗DBL 5 ε IgG与iRBC表面上VSA-PAM的IgG水平显著相关。HIV阳性妇女的抗DBL 5 ε IgG水平低于同等胎次的HIV阴性妇女。在孕妇中，HIV阳性女性中的抗体也显示出对VAR 2CSA DBL 5 ε的显著较低亲和力。来自疟疾流行区的孕妇经产时抗DBL 5 ε IgG水平增加，表明VAR 2CSA的该结构域是有希望的针对PAM的候选疫苗。然而，重要的是要考虑与艾滋病毒的共同感染，因为这似乎改变了对疟疾的抗体反应的性质。了解针对VAR 2CSA的抗体应答的特征对于设计针对PAM的功能性和有效的疫苗无疑是必要的。
Plasmodium falciparum infected red blood cells (iRBC) express variant surface antigens (VSA) of which VAR2CSA is involved in placental sequestration and causes pregnancy-associated malaria (PAM). Primigravidae are most susceptible to PAM whereas antibodies associated with protection are often present at higher levels in multigravid women. However, HIV co-infection with malaria has been shown to alter this parity-dependent acquisition of immunity, with more severe symptoms as well as more malaria episodes in HIV positive women versus HIV negative women of a similar parity. Using VAR2CSA DBL-domains expressed on the surface of CHO-745 cells we quantified levels of DBL-domain specific IgG in sera from pregnant Malawian women by flow cytometry. Dissociations constants of DBL5ε specific antibodies were determined using a surface plasmon resonance technique, as an indication of antibody affinities. VAR2CSA DBL5ε was recognized in a gender and parity-dependent manner with anti-DBL5ε IgG correlating significantly with IgG levels to VSA-PAM on the iRBC surface. HIV positive women had lower levels of anti-DBL5ε IgG than HIV negative women of similar parity. In primigravidae, antibodies in HIV positive women also showed significantly lower affinity to VAR2CSA DBL5ε. Pregnant women from a malaria-endemic area had increased levels of anti-DBL5ε IgG by parity, indicating this domain of VAR2CSA to be a promising vaccine candidate against PAM. However, it is important to consider co-infection with HIV, as this seems to change the properties of antibody response against malaria. Understanding the characteristics of antibody response against VAR2CSA is undoubtedly imperative in order to design a functional and efficient vaccine against PAM.
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