当前位置: X-MOL 学术Virus Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
SARS-CoV-2 specific memory T cell epitopes identified in COVID-19-recovered subjects
Virus Research ( IF 5 ) Pub Date : 2021-07-27 , DOI: 10.1016/j.virusres.2021.198508
Juan Zhao 1 , Ling Wang 1 , Madison Schank 1 , Xindi Dang 1 , Zeyuan Lu 2 , Dechao Cao 1 , Sushant Khanal 1 , Lam N Nguyen 1 , Lam N T Nguyen 1 , Jinyu Zhang 1 , Yi Zhang 1 , James L Adkins 2 , Evan M Baird 2 , Xiao Y Wu 1 , Shunbin Ning 1 , Mohamed El Gazzar 1 , Jonathan P Moorman 3 , Zhi Q Yao 3
Affiliation  

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to public health. An explicit investigation of COVID-19 immune responses, particularly the host immunity in recovered subjects, will lay a foundation for the rational design of therapeutics and/or vaccines against future coronaviral outbreaks. Here, we examined virus-specific T cell responses and identified T cell epitopes using peptides spanning SARS-CoV-2 structural proteins. These peptides were used to stimulate peripheral blood mononuclear cells (PBMCs) derived from COVID-19-recovered subjects, followed by an analysis of IFN-γ-secreting T cells by enzyme-linked immunosorbent spot (ELISpot). We also evaluated virus-specific CD4 or CD8 T cell activation by flow cytometry assay. By screening 52 matrix pools (comprised of 315 peptides) of the spike (S) glycoprotein and 21 matrix pools (comprised of 102 peptides) spanning the nucleocapsid (N) protein, we identified 28 peptides from S protein and 5 peptides from N protein as immunodominant epitopes. The immunogenicity of these epitopes was confirmed by a second ELISpot using single peptide stimulation in memory T cells, and they were mapped by HLA restrictions. Notably, SARS-CoV-2 specific T cell responses positively correlated with B cell IgG and neutralizing antibody responses to the receptor-binding domain (RBD) of the S protein. Our results demonstrate that defined levels of SARS-CoV-2 specific T cell responses are generated in some, but not all, COVID-19-recovered subjects, fostering hope for the protection of a proportion of COVID-19-exposed individuals against reinfection. These results also suggest that these virus-specific T cell responses may induce protective immunity in unexposed individuals upon vaccination, using vaccines generated based on the immune epitopes identified in this study. However, SARS-CoV-2 S and N peptides are not potently immunogenic, and none of the single peptides could universally induce robust T cell responses, suggesting the necessity of using a multi-epitope strategy for COVID-19 vaccine design.



中文翻译:

在 COVID-19 康复受试者中鉴定出 SARS-CoV-2 特异性记忆 T 细胞表位

由 SARS-CoV-2 感染引起的 COVID-19 大流行对公众健康构成严重威胁。对 COVID-19 免疫反应的明确研究,特别是康复受试者的宿主免疫,将为合理设计针对未来冠状病毒爆发的疗法和/或疫苗奠定基础。在这里,我们检查了病毒特异性 T 细胞反应,并使用跨越 SARS-CoV-2 结构蛋白的肽鉴定了 T 细胞表位。这些肽用于刺激源自 COVID-19 康复受试者的外周血单核细胞 (PBMC),然后通过酶联免疫吸附点 (ELISpot) 分析分泌 IFN-γ 的 T 细胞。我们还通过流式细胞术测定评估了病毒特异性 CD4 或 CD8 T 细胞活化。通过筛选刺突 (S) 糖蛋白的 52 个矩阵池(由 315 个肽组成)和跨越核衣壳 (N) 蛋白的 21 个矩阵池(由 102 个肽组成),我们从 S 蛋白中鉴定出 28 个肽,从 N 蛋白中鉴定出 5 个肽为免疫显性表位。这些表位的免疫原性通过在记忆 T 细胞中使用单肽刺激的第二个 ELISpot 确认,并且它们通过 HLA 限制性作图。值得注意的是,SARS-CoV-2 特异性 T 细胞反应与 B 细胞 IgG 和中和抗体对 S 蛋白受体结合域 (RBD) 的反应呈正相关。我们的结果表明,某些(但不是所有)COVID-19 康复受试者会产生一定水平的 SARS-CoV-2 特异性 T 细胞反应,为保护一部分暴露于 COVID-19 的个人免于再次感染带来希望。这些结果还表明,使用根据本研究中确定的免疫表位生成的疫苗,这些病毒特异性 T 细胞反应可能会在未暴露个体接种疫苗后诱导保护性免疫。然而,SARS-CoV-2 S 和 N 肽不具有强大的免疫原性,而且没有一种肽可以普遍诱导强烈的 T 细胞反应,这表明有必要使用多表位策略来设计 COVID-19 疫苗。

更新日期:2021-08-04
down
wechat
bug