Congling Qiu , Bo Peng , Chanchan Xiao , Pengfei Chen , Lipeng Mao , Xiaolu Shi , Zhen Zhang , Ziquan Lv , Qiuying Lv , Xiaomin Zhang , Jiaxin Li , Yanhao Huang , Qinghua Hu , Guobing Chen , Xuan Zou , Xiaofeng Liang
{"title":"A novel method for identifying SARS-CoV-2 infection mutants via an epitope-specific CD8+ T cell test","authors":"Congling Qiu , Bo Peng , Chanchan Xiao , Pengfei Chen , Lipeng Mao , Xiaolu Shi , Zhen Zhang , Ziquan Lv , Qiuying Lv , Xiaomin Zhang , Jiaxin Li , Yanhao Huang , Qinghua Hu , Guobing Chen , Xuan Zou , Xiaofeng Liang","doi":"10.1016/j.bsheal.2024.03.005","DOIUrl":null,"url":null,"abstract":"<div><p>Since the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in 2019, the public health system has faced enormous challenges. Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality. With the increasing of asymptomatic infections, it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing. However, due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes, neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2. We recruited 4 human leukocyte antigen A2 (HLA-A2) infections, 15 individuals who received three doses of inactivated vaccines, and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8<sup>+</sup> T cells in the peripheral blood of close contacts, including accurate HLA typing based on ribonucleic acid (RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8<sup>+</sup> T cells. From individuals who received three doses of inactivated vaccine, we observed that the CD8<sup>+</sup> T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes, and the fold change of CD8<sup>+</sup> T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1. The enzyme-linked immunospot (ELISpot) results further validate this result. This study forms a “method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8<sup>+</sup> T cells in the peripheral blood of subjects”, covering up to 46 % of the population, including HLA-A2<sup>+</sup> and HLA-A24<sup>+</sup> donors, providing a novel method for SARS-CoV-2 infected case tracing.</p></div>","PeriodicalId":36178,"journal":{"name":"Biosafety and Health","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590053624000326/pdfft?md5=f1efcb418ab5e241a7316a79df11a3a4&pid=1-s2.0-S2590053624000326-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biosafety and Health","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590053624000326","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH","Score":null,"Total":0}
引用次数: 0
Abstract
Since the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in 2019, the public health system has faced enormous challenges. Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality. With the increasing of asymptomatic infections, it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing. However, due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes, neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2. We recruited 4 human leukocyte antigen A2 (HLA-A2) infections, 15 individuals who received three doses of inactivated vaccines, and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8+ T cells in the peripheral blood of close contacts, including accurate HLA typing based on ribonucleic acid (RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8+ T cells. From individuals who received three doses of inactivated vaccine, we observed that the CD8+ T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes, and the fold change of CD8+ T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1. The enzyme-linked immunospot (ELISpot) results further validate this result. This study forms a “method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8+ T cells in the peripheral blood of subjects”, covering up to 46 % of the population, including HLA-A2+ and HLA-A24+ donors, providing a novel method for SARS-CoV-2 infected case tracing.