Oleinikov Andrew V, Rossnagle Eddie, Francis Susan, Mutabingwa Theonest K, Fried Michal, Duffy Patrick E
Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
J Infect Dis. 2007 Jul 1;196(1):155-64. doi: 10.1086/518513. Epub 2007 May 23.
Plasmodium falciparum-infected erythrocytes adhere to chondroitin sulfate A (CSA) to sequester in the human placenta, and pregnancy malaria (PM) is associated with the development of disease in and the death of both mother and child. A PM vaccine appears to be feasible, because women become protected as they develop antibodies against placental infected erythrocytes (IEs). Two IE surface molecules, VAR1CSA and VAR2CSA, bind CSA in vitro and are potential vaccine candidates.
We expressed all domains of VAR1CSA and VAR2CSA as mammalian cell surface proteins, using a novel approach that allows rapid purification, immobilization, and quantification of target antigen. For serum samples from East Africa, we measured reactivity to all domains, and we examined the effects of host sex and parity, as well as the effects of parasite antigenic variation.
Serum samples obtained from multigravid women had a higher reactivity to all VAR2CSA domains than did those obtained from primigravid women or from men. Conversely, serum samples obtained from men had consistently higher reactivity to VAR1CSA domains than did those obtained from gravid women. Seroreactivity was strongly influenced by antigenic variation of VAR2CSA Duffy binding-like domains.
Women acquire antibodies to VAR2CSA over successive pregnancies, but they lose reactivity to VAR1CSA. Serum reactivity to VAR2CSA is variant specific, and future studies should examine the degree to which functional antibodies, such as binding-inhibition antibodies, are variant specific.
恶性疟原虫感染的红细胞会黏附于硫酸软骨素A（CSA），从而在人胎盘内滞留，而妊娠疟疾（PM）与母婴疾病的发生及死亡有关。一种PM疫苗似乎是可行的，因为女性在产生针对胎盘感染红细胞（IEs）的抗体时会获得保护。两种IE表面分子，即VAR1CSA和VAR2CSA，在体外可结合CSA，是潜在的疫苗候选物。
我们采用一种新方法，将VAR1CSA和VAR2CSA的所有结构域表达为哺乳动物细胞表面蛋白，该方法可实现靶抗原的快速纯化、固定化及定量。对于来自东非的血清样本，我们检测了对所有结构域的反应性，并研究了宿主性别和胎次的影响，以及寄生虫抗原变异的影响。
与初孕女性或男性的血清样本相比，经产妇的血清样本对所有VAR2CSA结构域的反应性更高。相反，男性的血清样本对VAR1CSA结构域的反应性始终高于孕妇的血清样本。血清反应性受VAR2CSA达菲结合样结构域抗原变异的强烈影响。
女性在连续妊娠过程中会产生针对VAR2CSA的抗体，但会失去对VAR1CSA的反应性。血清对VAR2CSA的反应性具有变异特异性，未来的研究应考察功能性抗体（如结合抑制抗体）在多大程度上具有变异特异性。
