A novel method for identifying SARS-CoV-2 infection mutants via an epitope-specific CD8^(+)T cell test  

作　　者：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 

机构地区：[1]Department of Public Health and Preventive Medicine,School of Medicine,Jinan University,Kangtai Biological Vaccine Industry Research Institute/Disease Prevention and Control Institute of Jinan University,Guangzhou 510632,China [2]Shenzhen Center for Disease Control and Prevention,Shenzhen 518020,China [3]Department of Microbiology and Immunology,Institute of Geriatric Immunology,School of Medicine,Jinan University,Guangzhou 510632,China [4]Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University),Ministry of Education,Guangzhou 510632,China [5]The Sixth Affiliated Hospital,Jinan University,Guangzhou 510632,China [6]Department of Systems Biomedical Sciences,School of Medicine,Jinan University,Guangzhou 510632,China [7]Microbiology Laboratory,Shenzhen Center for Disease Control and Prevention,Shenzhen 518020,China [8]Department of Communicable Diseases Control and Prevention,Shenzhen Center for Disease Control and Prevention,Shenzhen 518020,China [9]Central Laboratory,Shenzhen Center for Disease Control and Prevention,Shenzhen 518020,China

出　　处：《Biosafety and Health》2024年第3期143-152,共10页生物安全与健康（英文）

基　　金：the Key Project of Shenzhen Science and Technology Innovation Commission(JCYJ20210324115411030);Natural Science Foundation of China(92169102);R&D Program of Guangzhou Laboratory(SRPG22-006);Sanming Project of Medicine in Shenzhen(SZSM202211023);GuangDong Basic and Applied Basic Research Foundation(2022B1515120043);the Open Project Fund of Guangdong Provincial People’s Hospital(YKY-KF202208);National Natural Science Foundation of China(81902097);Funding by Science and Technology Projects in Guangzhou(SL2023A04J01160);the Guangdong Basic and;Applied Basic Research Foundation(2023A1515140117);the fellowship of China Postdoctoral Science Foundation(2023TQ0136,2023M741379);supported by grants from the National Key Research and Development Plan(2023YFE0118700,2021YFC2301604);the Fundamental Research Funds for the Central Q4 Universities(21623406).

摘　　要：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.

关 键 词：Asymptomatic coronavirus disease 2019 (COVID-19) EPITOPES Specific CD8^(+)T cell ELISPOT 

分 类 号：R446.62[医药卫生—诊断学]