Sobarzo Ariel, Perelman Eddie, Groseth Allison, Dolnik Olga, Becker Stephan, Lutwama Julius Julian, Dye John M, Yavelsky Victoria, Lobel Leslie, Marks Robert S
Department of Virology & Developmental Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Clin Vaccine Immunol. 2012 Nov;19(11):1844-52. doi: 10.1128/CVI.00363-12. Epub 2012 Sep 19.
Ebolavirus, a member of the family Filoviridae, causes high lethality in humans and nonhuman primates. Research focused on protection and therapy for Ebola virus infection has investigated the potential role of antibodies. Recent evidence suggests that antibodies can be effective in protection from lethal challenge with Ebola virus in nonhuman primates. However, despite these encouraging results, studies have not yet determined the optimal antibodies and composition of an antibody cocktail, if required, which might serve as a highly effective and efficient prophylactic. To better understand optimal antibodies and their targets, which might be important for protection from Ebola virus infection, we sought to determine the profile of viral protein-specific antibodies generated during a natural cycle of infection in humans. To this end, we characterized the profile of antibodies against individual viral proteins of Sudan Ebola virus (Gulu) in human survivors and nonsurvivors of the outbreak in Gulu, Uganda, in 2000-2001. We developed a unique chemiluminescence enzyme-linked immunosorbent assay (ELISA) for this purpose based on the full-length recombinant viral proteins NP, VP30, and VP40 and two recombinant forms of the viral glycoprotein (GP(1-294) and GP(1-649)) of Sudan Ebola virus (Gulu). Screening results revealed that the greatest immunoreactivity was directed to the viral proteins NP and GP(1-649), followed by VP40. Comparison of positive immunoreactivity between the viral proteins NP, GP(1-649), and VP40 demonstrated a high correlation of immunoreactivity between these viral proteins, which is also linked with survival. Overall, our studies of the profile of immunorecognition of antibodies against four viral proteins of Sudan Ebola virus in human survivors may facilitate development of effective monoclonal antibody cocktails in the future.
埃博拉病毒是丝状病毒科的成员，可在人类和非人类灵长类动物中引发高致死率。针对埃博拉病毒感染的保护和治疗研究对抗体的潜在作用进行了调查。最近的证据表明，抗体在保护非人类灵长类动物免受埃博拉病毒致死性攻击方面可能有效。然而，尽管有这些令人鼓舞的结果，但研究尚未确定最佳抗体以及抗体鸡尾酒（如有需要）的组成，而抗体鸡尾酒可能是一种高效且有效的预防措施。为了更好地了解可能对预防埃博拉病毒感染很重要的最佳抗体及其靶点，我们试图确定人类自然感染周期中产生的病毒蛋白特异性抗体的情况。为此，我们对2000 - 2001年乌干达古卢埃博拉疫情中的人类幸存者和非幸存者体内针对苏丹埃博拉病毒（古卢株）各个病毒蛋白的抗体情况进行了表征。我们基于苏丹埃博拉病毒（古卢株）的全长重组病毒蛋白NP、VP30和VP40以及病毒糖蛋白的两种重组形式（GP(1 - 294)和GP(1 - 649)）开发了一种独特的化学发光酶联免疫吸附测定（ELISA）方法。筛选结果显示，最强的免疫反应性针对病毒蛋白NP和GP(1 - 649)，其次是VP40。对病毒蛋白NP、GP(1 - 649)和VP40之间阳性免疫反应性的比较表明，这些病毒蛋白之间的免疫反应性高度相关，这也与生存情况有关。总体而言，我们对人类幸存者体内针对苏丹埃博拉病毒四种病毒蛋白的抗体免疫识别情况的研究可能有助于未来开发有效的单克隆抗体鸡尾酒。
