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大规模鉴定严重急性呼吸综合征冠状病毒 2 衍生的 T 细胞表位,用于开发针对 2019 年冠状病毒病的肽疫苗。

Large-Scale Identification of T-Cell Epitopes Derived From Severe Acute Respiratory Syndrome Coronavirus 2 for the Development of Peptide Vaccines Against Coronavirus Disease 2019.

机构信息

Department of Research and Development, Shenzhen Institute for Innovation and Translational Medicine, Shenzhen International Biological Valley-Life Science Industrial Park, Dapeng New District, Shenzhen, China.

Department of Oncology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

出版信息

J Infect Dis. 2021 Sep 17;224(6):956-966. doi: 10.1093/infdis/jiab324.

Abstract

BACKGROUND

Coronavirus disease 2019 (COVID-19) continues to be a major public health challenge globally. The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived T-cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19.

METHODS

In this study, several SARS-CoV-2-derived human leukocyte antigen (HLA)-I binding peptides were predicted by NetMHCpan-4.1 and selected by Popcover to achieve pancoverage of the Chinese population. The top 5 ranked peptides derived from each protein of SARS-CoV-2 were then evaluated using peripheral blood mononuclear cells from unexposed individuals (negative for SARS-CoV-2 immunoglobulin G).

RESULTS

Seven epitopes derived from 4 SARS-CoV-2 proteins were identified. It is interesting to note that most (5 of 7) of the SARS-CoV-2-derived peptides with predicted affinities for HLA-I molecules were identified as HLA-II-restricted epitopes and induced CD4+ T cell-dependent responses. These results complete missing pieces of pre-existing SARS-CoV-2-specific T cells and suggest that pre-existing T cells targeting all SARS-CoV-2-encoded proteins can be discovered in unexposed populations.

CONCLUSIONS

In summary, in the current study, we present an alternative and effective strategy for the identification of T-cell epitopes of SARS-CoV-2 in healthy subjects, which may indicate an important role in the development of peptide vaccines for COVID-19.

摘要

背景

新型冠状病毒病 2019(COVID-19)仍然是全球主要的公共卫生挑战。鉴定严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)衍生的 T 细胞表位对于 COVID-19 的肽疫苗或诊断工具至关重要。

方法

在这项研究中,通过 NetMHCpan-4.1 预测了几种 SARS-CoV-2 衍生的人类白细胞抗原(HLA)-I 结合肽,并通过 Popcover 进行选择,以实现对中国人群的全覆盖。然后,使用未暴露个体(SARS-CoV-2 免疫球蛋白 G 阴性)的外周血单核细胞评估源自 SARS-CoV-2 每种蛋白的前 5 个排名肽。

结果

从 4 种 SARS-CoV-2 蛋白中鉴定出 7 个表位。有趣的是,大多数(7 个中的 5 个)具有预测亲和力的 SARS-CoV-2 衍生肽被鉴定为 HLA-II 限制性表位,并诱导 CD4+T 细胞依赖性反应。这些结果完整地揭示了先前存在的 SARS-CoV-2 特异性 T 细胞的缺失部分,并表明可以在未暴露人群中发现针对所有 SARS-CoV-2 编码蛋白的预先存在的 T 细胞。

结论

总之,在目前的研究中,我们提出了一种鉴定健康受试者中 SARS-CoV-2 T 细胞表位的替代且有效的策略,这可能表明在开发 COVID-19 肽疫苗方面具有重要作用。

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