Institute for Infectious Diseases and Zoonoses, LMU Munich, 80539 Munich, Germany.
German Center for Infection Research (DZIF), partner site Munich, 80539 Munich, Germany.
Viruses. 2018 Dec 16;10(12):718. doi: 10.3390/v10120718.
Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and in mediating vaccine-induced protective immunity. In contrast, relatively little is known about the role of T cell responses and the antigenic targets of MERS-CoV that are recognized by CD8+ T cells. In this study, the highly conserved MERS-CoV nucleocapsid (N) protein served as a target immunogen to elicit MERS-CoV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for generating MVA-MERS-N expressing recombinant N protein. Overlapping peptides spanning the whole MERS-CoV N polypeptide were used to identify major histocompatibility complex class I/II-restricted T cell responses in BALB/c mice immunized with MVA-MERS-N. We have identified a H2-d restricted decamer peptide epitope in the MERS-N protein with CD8+ T cell antigenicity. The identification of this epitope, and the availability of the MVA-MERS-N candidate vaccine, will help to evaluate MERS-N-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of MERS-CoV infection.
中东呼吸综合征冠状病毒(MERS-CoV)是一种新型的传染性病原体,可导致人类严重的呼吸道疾病和死亡,于 2012 年首次被描述。针对 MERS-CoV 刺突(S)蛋白的抗体被认为在控制 MERS-CoV 感染和介导疫苗诱导的保护性免疫方面发挥着重要作用。相比之下,人们对 T 细胞反应和 MERS-CoV 中被 CD8+T 细胞识别的抗原靶标知之甚少。在这项研究中,高度保守的 MERS-CoV 核衣壳(N)蛋白被用作靶免疫原,以引发 MERS-CoV 特异性细胞免疫反应。改良安卡拉痘苗病毒(MVA)是一种用于临床前和临床疫苗研究的安全性测试的痘苗病毒株,用于生成表达重组 N 蛋白的 MVA-MERS-N。使用跨越整个 MERS-CoV N 多肽的重叠肽来鉴定用 MVA-MERS-N 免疫的 BALB/c 小鼠中的主要组织相容性复合体 I/II 限制性 T 细胞反应。我们已经在 MERS-N 蛋白中鉴定出一个与 CD8+T 细胞抗原性相关的 H2-d 限制性十肽表位。该表位的鉴定以及 MVA-MERS-N 候选疫苗的可用性,将有助于在适当的 MERS-CoV 感染的小鼠模型中评估 MERS-N 特异性免疫反应和疫苗介导保护的潜在免疫相关性。