Baruch Dror I, Gamain Benoit, Barnwell John W, Sullivan JoAnn S, Stowers Anthony, Galland G Gale, Miller Louis H, Collins William E
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3860-5. doi: 10.1073/pnas.022018399.
Immunity to Plasmodium falciparum in African children has been correlated with antibodies to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) variant gene family expressed on the surface of infected red cells. We immunized Aotus monkeys with a subregion of the Malayan Camp variant antigen (MCvar1) that mediates adhesion to the host receptor CD36 on the endothelial surface and present data that PfEMP1 is an important target for vaccine development. The immunization induced a high level of protection against the homologous strain. Protection correlated with the titer of agglutinating antibodies and occurred despite the expression of variant copies of the gene during recurrent waves of parasitemia. A second challenge with a different P. falciparum strain, to which there was no agglutinating activity, showed no protection but boosted the immune response to this region during the infection. The level of protection and the evidence of boosting during infection encourage further exploration of this concept for malaria vaccine development.
非洲儿童对恶性疟原虫的免疫力与针对感染红细胞表面表达的恶性疟原虫红细胞膜蛋白1（PfEMP1）变异基因家族的抗体相关。我们用马来亚营地变异抗原（MCvar1）的一个亚区域免疫夜猴，该亚区域介导与内皮表面宿主受体CD36的粘附，并提供数据表明PfEMP1是疫苗开发的重要靶点。免疫诱导了对同源菌株的高水平保护。保护作用与凝集抗体滴度相关，尽管在反复的寄生虫血症波期间基因的变异拷贝表达，但仍发生了保护作用。用一种没有凝集活性的不同恶性疟原虫菌株进行的第二次攻击没有显示出保护作用，但在感染期间增强了对该区域的免疫反应。保护水平和感染期间增强的证据鼓励进一步探索这一概念用于疟疾疫苗开发。
