Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2010 Feb 16;5(2):e9230. doi: 10.1371/journal.pone.0009230.
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 DBL5epsilon specific antibodies were determined using a surface plasmon resonance technique, as an indication of antibody affinities.
VAR2CSA DBL5epsilon was recognized in a gender and parity-dependent manner with anti-DBL5epsilon IgG correlating significantly with IgG levels to VSA-PAM on the iRBC surface. HIV positive women had lower levels of anti-DBL5epsilon IgG than HIV negative women of similar parity. In primigravidae, antibodies in HIV positive women also showed significantly lower affinity to VAR2CSA DBL5epsilon.
Pregnant women from a malaria-endemic area had increased levels of anti-DBL5epsilon 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.
恶性疟原虫感染的红细胞（iRBC）表达变异表面抗原（VSA），其中 VAR2CSA 参与胎盘定殖并导致妊娠相关疟疾（PAM）。初产妇最易感染 PAM，而与保护相关的抗体通常在多产妇中的水平更高。然而，疟疾合并 HIV 感染已被证明会改变这种与生育次数相关的免疫获得方式，与 HIV 阴性的同一生育次数的妇女相比，HIV 阳性妇女的症状更严重，疟疾发作次数更多。
我们使用表达在 CHO-745 细胞表面的 VAR2CSA DBL 结构域，通过流式细胞术定量了来自马拉维孕妇血清中 DBL 结构域特异性 IgG 的水平。使用表面等离子体共振技术确定了 DBL5epsilon 特异性抗体的解离常数，作为抗体亲和力的指标。
VAR2CSA DBL5epsilon 的识别具有性别和生育次数依赖性，抗-DBL5epsilon IgG 与 iRBC 表面 VSA-PAM 的 IgG 水平显著相关。与相似生育次数的 HIV 阴性妇女相比，HIV 阳性妇女的抗-DBL5epsilon IgG 水平较低。在初产妇中，HIV 阳性妇女的抗体对 VAR2CSA DBL5epsilon 的亲和力也显著降低。
来自疟疾流行地区的孕妇按生育次数增加了抗-DBL5epsilon IgG 的水平，表明该 VAR2CSA 结构域是预防 PAM 的有前途的疫苗候选物。然而，考虑到 HIV 合并感染很重要，因为这似乎改变了针对疟疾的抗体反应特性。了解针对 VAR2CSA 的抗体反应特征对于设计针对 PAM 的功能性和有效的疫苗无疑是至关重要的。
