Seattle Biomedical Research Institute, Seattle, WA, USA.
Infect Immun. 2013 Feb;81(2):487-95. doi: 10.1128/IAI.01106-12. Epub 2012 Dec 3.
Pregnancy malaria is caused by Plasmodium falciparum-infected erythrocytes that adhere to the placental receptor chondroitin sulfate A (CSA) and sequester in the placenta; women become resistant to pregnancy malaria as they acquire antiadhesion antibodies that target surface proteins of placental parasites. VAR2CSA, a member of the P. falciparum EMP1 variant surface antigen family, is the leading candidate for a pregnancy malaria vaccine. Because VAR2CSA is a high-molecular-weight protein, a vaccine based on the full-length protein may not be feasible. An alternative approach has been to develop a vaccine targeting individual Duffy binding-like (DBL) domains. In this study, a consortium of laboratories under the Pregnancy Malaria Initiative compared the functional activity of antiadhesion antibodies elicited by different VAR2CSA domains and variants produced in prokaryotic and eukaryotic expression systems. Antisera were initially tested against laboratory lines of maternal parasites, and the most promising reagents were evaluated in the field against fresh placental parasite samples. Recombinant proteins expressed in Escherichia coli elicited antibody levels similar to those expressed in eukaryotic systems, as did the two allelic forms of the DBL4 and DBL5 domains. The procedures developed for this head-to-head comparison will be useful for future evaluation and down-selection of malaria vaccine immunogens.
妊娠疟疾是由感染疟原虫的红细胞引起的，这些红细胞黏附在胎盘受体硫酸软骨素 A（CSA）上，并在胎盘内隐匿；女性在获得针对胎盘寄生虫表面蛋白的抗黏附抗体后，会对妊娠疟疾产生抵抗力。VAR2CSA 是恶性疟原虫 EMP1 变体表面抗原家族的成员，是妊娠疟疾疫苗的主要候选者。由于 VAR2CSA 是一种高分子量蛋白，基于全长蛋白的疫苗可能不可行。另一种方法是开发针对个体 Duffy 结合样（DBL）结构域的疫苗。在这项研究中，妊娠疟疾计划下的一个实验室联盟比较了不同 VAR2CSA 结构域和在原核及真核表达系统中产生的变体所引起的抗黏附抗体的功能活性。抗血清最初针对实验室来源的母体寄生虫系进行了测试，最有前途的试剂在现场针对新鲜胎盘寄生虫样本进行了评估。在大肠杆菌中表达的重组蛋白引起的抗体水平与在真核系统中表达的水平相似，DBL4 和 DBL5 结构域的两种等位形式也是如此。为进行这种直接比较而开发的程序将有助于未来对疟疾疫苗免疫原进行评估和选择。
