Yang S, Carroll M W, Torres-Duarte A P, Moss B, Davidson E A
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, NW Washington, DC 20007, USA.
Vaccine. 1997 Aug-Sep;15(12-13):1303-13. doi: 10.1016/s0264-410x(97)00039-x.
Genes encoding four different C-terminal fragments of a Plasmodium falciparum merozoite surface antigen were generated: MSA1C-(Si,A), containing signal and anchor regions of MSA1; MSA1C-(Si,nA), containing the signal but not the anchor; MSA1C-(nSi,A), containing the anchor but not the signal, and MSA1C-(nSi,nA) containing neither the signal nor the anchor region. Each gene was inserted into the thymidine kinase region of vaccinia virus, under the control of a synthetic strong early/ late promoter. When the plasmodial genes were expressed in cells infected by the recombinant vaccinia virus, the two proteins containing the signal region were transported to the surface of infected cells. Infection of mice and rabbits with the latter recombinant viruses stimulated C-terminal-specific antibody levels that were 10-80-fold higher than those induced by the two recombinant viruses without the signal region. The combination of the signal and anchor regions with the C-terminal MSA1 protein also generated the most effective neutralization in a P. falciparum invasion assay.
构建了编码恶性疟原虫裂殖子表面抗原四种不同C末端片段的基因：MSA1C-(Si,A)，包含MSA1的信号和锚定区域；MSA1C-(Si,nA)，包含信号但不包含锚定区域；MSA1C-(nSi,A)，包含锚定区域但不包含信号；以及MSA1C-(nSi,nA)，既不包含信号区域也不包含锚定区域。每个基因都在合成的强早期/晚期启动子的控制下插入痘苗病毒的胸苷激酶区域。当疟原虫基因在重组痘苗病毒感染的细胞中表达时，两种包含信号区域的蛋白质被转运到感染细胞的表面。用后两种重组病毒感染小鼠和兔子，刺激产生的C末端特异性抗体水平比由没有信号区域的两种重组病毒诱导产生的抗体水平高10 - 80倍。在恶性疟原虫入侵试验中，信号和锚定区域与C末端MSA1蛋白的组合也产生了最有效的中和作用。
