新加坡国立大学的研究人员发现，一种对血清型2登革热病毒的人类抗体(被称作2D22)可保护小鼠不受一种致命型登革热病毒的侵害，他们表示，2D22与该登革热病毒结合的位点可能会是一种潜在的疫苗标靶。这种蚊媒病毒每年在全球会感染近4亿人，它有4种不同的血清型(或抗原变异)，目前还没有一种具有保护性的疫苗。最近对一种可能的候选疫苗的3期临床试验显示其功效不佳，尤其是对血清型2登革热病毒效果不佳。Guntur Fibriansah和同事发现，2D22可保护小鼠免受血清型2登革热病毒侵害，且无论是在小鼠接种病毒之前还是之后给予该抗体都具保护性。这一结果表明，该抗体可能同时是一种预防性制剂和一种治疗性制剂。为了得到更多的了解，研究人员分析了低温电子显微镜(cryo-EM)下所见的分辨率在6.5和7.0埃之间的2D22与两个不同血清型2(这种血清型具有最活跃的表面)登革热病毒株所形成的复合物的结构。这些cryo-EM结构揭示，2D22会与病毒包膜蛋白结合，将其大约三分之二锁定在病毒表面，并阻止它们重组成进入宿主细胞所需的取向。

 

    原文链接：Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers

 

    原文摘要：There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)–specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo–electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 “locks” two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.