Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
US Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, MD 21702-5011, USA.
EBioMedicine. 2019 Aug;46:215-226. doi: 10.1016/j.ebiom.2019.07.021. Epub 2019 Jul 17.
Profiles of immunity developed in filovirus patients and survivors have begun to shed light on antigen-specific cellular immune responses that had been previously under-studied. However, our knowledge of the breadth and length of those responses and the viral targets which mediate long-term memory immunity still lags significantly behind.
We characterized antigen-specific immune responses in whole blood samples of fifteen years post-infected survivors of the Sudan virus (SUDV) outbreak in Gulu, Uganda (2000-2001). We examined T cell and IgG responses against SUDV complete antigen and four SUDV proteins; glycoprotein (GP), nucleoprotein (NP), and viral protein 30 (VP30), and 40 (VP40).
We found survivors-maintained antigen-specific CD4+ T cell memory immune responses mediated mainly by the viral protein NP. In contrast, activated CD8+ T cell responses were nearly absent in SUDV survivors, regardless of the stimulating antigen used. Analysis of anti-viral humoral immunity revealed antigen-specific IgG antibodies against SUDV and SUDV proteins. Survivor IgGs mediated live SUDV neutralization in vitro and FcγRI and FcγRIII antibody Fc-dependent responses, mainly via antibodies to the viral proteins GP and VP40.
We highlight the key role of several proteins, i.e., GP, NP, and VP40, to act as mediators of distinctive and sustained cellular memory immune responses in long-term SUDV survivors. We suggest that the inclusion of these viral proteins in vaccine development may best mimic survivor native memory immune responses with the potential of protecting against viral infection.
This research was funded by the Defense Threat Reduction Agency (CB4088) and by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R01AI111516. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
在丝状病毒患者和幸存者中所建立的免疫特征，开始阐明之前研究较少的抗原特异性细胞免疫反应。然而，我们对于这些反应的广度和长度以及介导长期记忆免疫的病毒靶点的了解仍然严重滞后。
我们在 15 年后对乌干达古卢爆发的苏丹丝状病毒（SUDV）（2000-2001 年）幸存者的全血样本进行了抗原特异性免疫反应的特征分析。我们检查了针对 SUDV 完整抗原和四个 SUDV 蛋白（糖蛋白（GP）、核蛋白（NP）和病毒蛋白 30（VP30）和 40（VP40）的 T 细胞和 IgG 反应。
我们发现幸存者维持了抗原特异性 CD4+T 细胞记忆免疫反应，主要由病毒蛋白 NP 介导。相比之下，无论使用何种刺激抗原，SUDV 幸存者的激活 CD8+T 细胞反应几乎不存在。对抗病毒体液免疫的分析显示，针对 SUDV 和 SUDV 蛋白存在抗原特异性 IgG 抗体。幸存者 IgG 在体外介导了活 SUDV 中和作用，以及 FcγRI 和 FcγRIII 抗体 Fc 依赖性反应，主要通过针对病毒蛋白 GP 和 VP40 的抗体。
我们强调了几种蛋白（即 GP、NP 和 VP40）的关键作用，它们作为长期 SUDV 幸存者中独特和持续的细胞记忆免疫反应的介质。我们建议在疫苗开发中纳入这些病毒蛋白可能会最好地模拟幸存者的天然记忆免疫反应，从而有潜力预防病毒感染。
这项研究由国防威胁降低局（CB4088）和美国国立卫生研究院过敏和传染病研究所资助，项目编号为 R01AI111516。内容仅由作者负责，不一定代表美国国立卫生研究院的官方观点。
