Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-0436, USA.
Virology. 2012 Jan 20;422(2):386-92. doi: 10.1016/j.virol.2011.10.020. Epub 2011 Dec 5.
The envelope (E) protein is composed of three domains (ED1, ED2 and ED3) with ED3 targeted by the most potent neutralizing antibodies. DENV-2 strains can be divided into six genotypes. Comparison of ED3 of representative strains of the six genotypes revealed that there are nine variable residues that are specific to a given genotype. Recombinant ED3s (rED3s) of six different DENV-2 strains representing all nine variable residues were expressed, and their reactivity against a panel of two DENV-2 type-specific and three DENV complex-reactive monoclonal antibodies (mAbs) were compared. The differences in binding affinity to the rED3s representing different DENV-2 genotypes were relatively small, with the exception of type-specific-mAb 3H5 that showed up to 10-fold differences in binding between genotypes. Overall the binding differences did not lead to detectable differences in neutralization. Based on these results, DENV-2 ED3-specific neutralizing antibodies will likely be effective against DENV-2 strains from all six genotypes.
包膜(E)蛋白由三个结构域(ED1、ED2 和 ED3)组成,其中 ED3 是最有效的中和抗体的靶标。登革热病毒 2 型可分为六个基因型。对六个基因型的代表性毒株的 ED3 进行比较,发现有九个特定于特定基因型的可变残基。表达了六个不同登革热病毒 2 型毒株的重组 ED3(rED3),并比较了它们与一组两株登革热病毒 2 型特异性和三株登革热病毒复合物反应性单克隆抗体(mAb)的反应性。除了与基因型之间的结合差异高达 10 倍的型特异性单抗 3H5 外,代表不同登革热病毒 2 型基因型的 rED3 的结合亲和力差异相对较小。总体而言,结合差异并未导致中和作用的可检测差异。基于这些结果,登革热病毒 2 型 ED3 特异性中和抗体可能对来自所有六个基因型的登革热病毒 2 型菌株有效。