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首页> 外文期刊>Infection and immunity >Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA
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Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

机译：妊娠相关疟疾疫苗候选VAR2CSA中全球共享的，交叉反应的多态性表位的证据

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Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of Plasmodium falciparum-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size (～350 kDa) and extensive polymorphism may pose a challenge to vaccine development. In this study, rabbits were immunized with individual VAR2CSA Duffy binding-like (DBL) domains expressed in Pichia pastoris or var2csa plasmid DNA and sera were screened on different CSA-binding parasite lines. Rabbit antibodies to three recombinant proteins (DBL1, DBL3, and DBL6) and four plasmid DNAs (DBL1, DBL3, DBL5, and DBL6) reacted with homologous FCR3-CSA IEs. By comparison, antibodies to the DBL4 domain were unable to react with native VAR2CSA protein unless it was first partially proteolyzed with trypsin or chymotrypsin. To investigate the antigenic relationship of geographically diverse CSA-binding isolates, rabbit immune sera were screened on four heterologous CSA-binding lines from different continental origins. Antibodies did not target conserved epitopes exposed in all VAR2CSA alleles; however, antisera to several DBL domains cross-reacted on parasite isolates that had polymorphic loops in common with the homologous immunogen. This study demonstrates that VAR2CSA contains common polymorphic epitopes that are shared between geographically diverse CSA-binding lines.
机译：怀孕相关的疟疾（PAM）的特征是胎盘隔离了恶性疟原虫感染的红细胞（IEs），并具有与硫酸软骨素A（CSA）结合的能力。 VAR2CSA是妊娠疟疾疫苗的主要候选药物，但其大尺寸（〜350 kDa）和广泛的多态性可能对疫苗的开发构成挑战。在这项研究中，兔用巴斯德毕赤酵母或 var2csa 质粒DNA中表达的单个VAR2CSA达菲结合样（DBL）结构域免疫，并在不同的CSA结合寄生虫上筛选血清线。抗三种重组蛋白（DBL1，DBL3和DBL6）和四种质粒DNA（DBL1，DBL3，DBL5和DBL6）的兔抗体与同源FCR3-CSA IEs反应。相比之下，除非先用胰蛋白酶或胰凝乳蛋白酶部分水解，否则针对DBL4结构域的抗体将无法与天然VAR2CSA蛋白反应。为了研究地理上不同的CSA结合分离物的抗原关系，在来自不同大陆的四个异源CSA结合系上筛选了兔免疫血清。抗体未针对所有VAR2CSA等位基因中暴露的保守表位。然而，针对几个DBL域的抗血清在具有与同源免疫原相同的多态性环的寄生虫分离物中交叉反应。这项研究表明VAR2CSA包含共同的多态性表位，在地理上不同的CSA结合系之间共享。

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