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CD8+ T 细胞对痘苗病毒 MVA 递送的中东呼吸综合征冠状病毒核衣壳蛋白的反应。

CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice.

机构信息

Institute for Infectious Diseases and Zoonoses, LMU Munich, 80539 Munich, Germany.

German Center for Infection Research (DZIF), partner site Munich, 80539 Munich, Germany.

出版信息

Viruses. 2018 Dec 16;10(12):718. doi: 10.3390/v10120718.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/156a/6316859/c0f97ff2d566/viruses-10-00718-g001.jpg

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