Gamain B, Miller L H, Baruch D I
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Drive MSC 0425, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2664-9. doi: 10.1073/pnas.041602598. Epub 2001 Feb 13.
Plasmodium falciparum parasites evade the host immune system by clonal expression of the variant antigen, P. falciparum erythrocyte membrane protein 1 (PfEMP1). Antibodies to PfEMP1 correlate with development of clinical immunity but are predominantly variant-specific. To overcome this major limitation for vaccine development, we set out to identify cross-reactive epitopes on the surface of parasitized erythrocytes (PEs). We prepared mAbs to the cysteine-rich interdomain region 1 (CIDR1) of PfEMP1 that is functionally conserved for binding to CD36. Two mAbs, targeting different regions of CIDR1, reacted with multiple P. falciparum strains expressing variant PfEMP1s. One of these mAbs, mAb 6A2-B1, recognized nine of 10 strains tested, failing to react with only one strain that does not bind CD36. Flow cytometry with Chinese hamster ovary cells expressing variant CIDR1s demonstrated that both mAbs recognized the CIDR1 of various CD36-binding PfEMP1s and are truly cross-reactive. The demonstration of cross-reactive epitopes on the PE surface provides further credence for development of effective vaccines against the variant antigen on the surface of P. falciparum-infected erythrocytes.
恶性疟原虫通过克隆表达变异抗原——恶性疟原虫红细胞膜蛋白1（PfEMP1）来逃避宿主免疫系统。针对PfEMP1的抗体与临床免疫的发展相关，但主要是变异特异性的。为了克服疫苗开发的这一主要限制，我们着手鉴定被寄生红细胞（PEs）表面的交叉反应性表位。我们制备了针对PfEMP1富含半胱氨酸的结构域间区域1（CIDR1）的单克隆抗体，该区域在功能上对于结合CD36是保守的。两种靶向CIDR1不同区域的单克隆抗体与表达变异PfEMP1的多种恶性疟原虫菌株发生反应。其中一种单克隆抗体mAb 6A2-B1识别了所测试的10种菌株中的9种，仅不与一种不结合CD36的菌株发生反应。用表达变异CIDR1的中国仓鼠卵巢细胞进行的流式细胞术表明，这两种单克隆抗体都识别各种结合CD36的PfEMP1的CIDR1，并且是真正的交叉反应性的。PE表面交叉反应性表位的证明为开发针对恶性疟原虫感染红细胞表面变异抗原的有效疫苗提供了进一步的可信度。
