West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Research and Transformation Center for Poisoning Treatment, Laboratory Science & Precision Prevention and Treatment, West China-PUMC C.C. Chen Institute of Health, Sichuan University, Chengdu, China.
Front Immunol. 2022 Jan 28;13:752622. doi: 10.3389/fimmu.2022.752622. eCollection 2022.
The current coronavirus disease 2019 (COVID-19) vaccines are used to prevent viral infection by inducing neutralizing antibody in the body, but according to the existing experience of severe acute respiratory syndrome coronavirus (SARS) infection, T-cell immunity could provide a longer durable protection period than antibody. The research on SARS-CoV-2-specific T-cell epitope can provide target antigen for the development and evaluation of COVID-19 vaccines, which is conducive to obtain COVID-19 vaccine that can provide long-term protection. For screening specific T-cell epitopes, a SARS-CoV-2 S protein peptide library with a peptide length of 15 amino acids was synthesized. Through flow cytometry to detect percentage of IFN-γ T cells after mixed COVID-19 convalescent patients' peripheral blood mononuclear cell with peptide library, seven peptides (P77, P14, P24, P38, P48, P74, and P84) that can be recognized by the T cells of COVID-19 convalescent patients were found. After excluding the nonspecific cross-reactions with unexposed population, three SARS-CoV-2-specific T-cell potential epitopes (P38, P48, and P84) were finally screened with the positive reaction rates between 15.4% and 48.0% in COVID-19 convalescent patients. This study also provided the HLA allele information of peptide-positive-response COVID-19 convalescent patients, thus predicting the population coverage of these three potential epitopes. Some HLA alleles showed higher frequency of occurrence in COVID-19 patients than in total Chinese population but no HLA alleles related to the T-cell peptide response and the severity of COVID-19. This research provides three potential T-cell epitopes that are helpful for the design and efficacy evaluation of COVID-19 vaccines. The HLA information provided by this research supplies reference significance for subsequent research such as finding the relation of HLA genotype with disease susceptibility.
当前的 2019 年冠状病毒病(COVID-19)疫苗用于通过在体内诱导中和抗体来预防病毒感染,但根据严重急性呼吸系统综合征冠状病毒(SARS)感染的现有经验,T 细胞免疫提供的保护期可能比抗体更长。对 SARS-CoV-2 特异性 T 细胞表位的研究可为 COVID-19 疫苗的开发和评估提供靶抗原,有利于获得能提供长期保护的 COVID-19 疫苗。为了筛选特异性 T 细胞表位,合成了一个长度为 15 个氨基酸的 SARS-CoV-2 S 蛋白肽文库。通过流式细胞术检测混合 COVID-19 康复患者外周血单个核细胞与肽文库后 IFN-γ T 细胞的百分比,发现了七种可被 COVID-19 康复患者 T 细胞识别的肽(P77、P14、P24、P38、P48、P74 和 P84)。在排除与未暴露人群的非特异性交叉反应后,最终筛选出三个 SARS-CoV-2 特异性 T 细胞潜在表位(P38、P48 和 P84),在 COVID-19 康复患者中的阳性反应率在 15.4%至 48.0%之间。这项研究还为肽阳性反应 COVID-19 康复患者提供了 HLA 等位基因信息,从而预测了这三个潜在表位的人群覆盖范围。一些 HLA 等位基因在 COVID-19 患者中的出现频率高于中国总人口,但没有与 T 细胞肽反应和 COVID-19 严重程度相关的 HLA 等位基因。这项研究提供了三个潜在的 T 细胞表位,有助于 COVID-19 疫苗的设计和疗效评估。本研究提供的 HLA 信息为后续研究,如寻找 HLA 基因型与疾病易感性的关系,提供了参考意义。