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Article(id=1199335103752139049, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199335100786766058, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.0075.2023.0427, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1673625600000, receivedDateStr=2023-01-14, revisedDate=null, revisedDateStr=null, acceptedDate=1678204800000, acceptedDateStr=2023-03-08, onlineDate=1763873371303, onlineDateStr=2025-11-23, pubDate=1709049600000, pubDateStr=2024-02-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763873371303, onlineIssueDateStr=2025-11-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763873371303, creator=13701087609, updateTime=1763873371303, updator=13701087609, issue=Issue{id=1199335100786766058, tenantId=1146029695717560320, journalId=1189873630562394117, year='2024', volume='49', issue='2', pageStart='123', pageEnd='244', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763873370596, creator=13701087609, updateTime=1763874072387, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1199338044361896535, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199335100786766058, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1199338044361896536, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199335100786766058, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=165, endPage=170, ext={EN=ArticleExt(id=1199335104045740340, articleId=1199335103752139049, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Characteristics of T cell immune responses in adults inoculated with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months. Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine. The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers (AIM) based on polychromatic flow cytometry. Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine, more than 90% of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses (Spike: 14/15, P=0.0001; Non-spike: 15/15, P<0.0001). 80% of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses (Spike: 12/15, P=0.0463; Non-spike: 12/15, P=0.0806). Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory (CM) and effector memory 1 (EM1) cells. On the other hand, in terms of helper subsets, antigen-specific CD4+ T cells mainly showed T helper 1/17 (Th1/17) and T helper 2 (Th2) phenotypes. Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses, which may be the key factor for the low proportion of severe coronavirus disease 2019 (COVID-19) infection in China.

, correspAuthors=Xing Fan, Fu-Sheng Wang, authorNote=null, correspAuthorsNote=
Wang Fu-Sheng, E-mail:
Fan Xing, E-mail:
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目的 评估成年人接种新型冠状病毒(SARS-CoV-2)灭活疫苗12个月后不同抗原特异性T细胞免疫应答的特点。方法 解放军总医院第五医学中心2022年4-6月招募15名健康成年人，于接种2剂新冠灭活疫苗12个月后采集其静脉血标本，以基于多色流式细胞术的活化诱导标记法(AIM)检测SARS-CoV-2抗原特异性T淋巴细胞水平，并分析其记忆表型与亚群分化特点。结果 成年人接种2剂灭活疫苗12个月后，90%以上个体可检测到Spike及Non-spike特异性CD4+ T细胞反应(S：14/15，P=0.0001；NS：15/15，P<0.0001)；80%个体检测到Spike及Non-spike特异性CD8+ T细胞反应(S：12/15，P=0.0463；NS：12/15，P=0.0806)。抗原特异性CD4+ T细胞主要表现为中央记忆细胞(CM)、1型效应记忆细胞(EM1)记忆表型，以及1/17型辅助性T细胞(Th1/17)、2型辅助性T细胞(Th2)辅助表型。结论 灭活疫苗接种后能诱导广泛且持久的抗原特异性CD4+ T细胞反应，可能是当前国内新型冠状病毒感染重症化比例较低的关键因素。

, correspAuthors=范兴, 王福生, authorNote=null, correspAuthorsNote=
王福生，E-mail：
范兴，E-mail：
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王静，硕士研究生，主要从事新冠疫苗免疫应答方面的研究

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王静，硕士研究生，主要从事新冠疫苗免疫应答方面的研究

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王静，硕士研究生，主要从事新冠疫苗免疫应答方面的研究

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A. 流式细胞术圈门策略图；B.各组抗原特异性T细胞频率比较；*P<0.05

, figureFileSmall=SLz2mS9neNzWZOEMYRYugw==, figureFileBig=2sL5tE58eOTZLa8f90VknA==, tableContent=null), ArticleFig(id=1199335111947809410, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1199335103752139049, language=EN, label=Fig.2, caption=Phenotypic characteristics of memory CD4+ T cells in adults after vaccination, figureFileSmall=+3K8TBWBPUnse2fUMnBZhQ==, figureFileBig=ni/jkrUKSqlGIiIKPbZQSA==, tableContent=null), ArticleFig(id=1199335112056861318, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1199335103752139049, language=CN, label=图2, caption=成年人接种疫苗后记忆性CD4+ T细胞表型特点

EMRA. RA+效应记忆细胞；CM. 中央记忆细胞；EM. 效应记忆细胞；A. 流式细胞术圈门策略图；B. 各组抗原特异性T细胞5类记忆表型频率比较；*P<0.05

, figureFileSmall=+3K8TBWBPUnse2fUMnBZhQ==, figureFileBig=ni/jkrUKSqlGIiIKPbZQSA==, tableContent=null), ArticleFig(id=1199335112170107530, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1199335103752139049, language=EN, label=Fig.3, caption=Phenotypic characteristics of memory CD4+ T cells in adults after vaccination, figureFileSmall=iazRNzaBV/GnWVXDxqbRnw==, figureFileBig=Df2VnPEWiCQIysDARVHAMA==, tableContent=null), ArticleFig(id=1199335112283353741, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1199335103752139049, language=CN, label=图3, caption=成年人接种疫苗后辅助性CD4+ T细胞表型特点

TFH. 滤泡辅助性T细胞；Th. 辅助性T细胞；A. 流式细胞术圈门策略图；B. 各组抗原特异性T细胞5类辅助亚群频率比较；*P<0.05

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成人接种2剂新冠灭活疫苗12个月后T细胞免疫应答特点
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王静 1, 2 , 李亚群 1, 2 , 汪海燕 1, 2 , 宋曜如 2 , 李静 2, 3 , 王文鑫 2, 3 , 万林钰 1, 2 , 周春保 2 , 范兴 2, * , 王福生 1, 2, *
解放军医学杂志 | 临床研究 2024,49(2): 165-170
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解放军医学杂志 | 临床研究 2024, 49(2): 165-170
成人接种2剂新冠灭活疫苗12个月后T细胞免疫应答特点
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王静1, 2, 李亚群1, 2, 汪海燕1, 2, 宋曜如2, 李静2, 3, 王文鑫2, 3, 万林钰1, 2, 周春保2, 范兴2, * , 王福生1, 2, *
作者信息
  • 1中国科学技术大学附属第一医院，安徽合肥 230001
  • 2解放军总医院第五医学中心感染病医学部/国家感染性疾病临床医学研究中心，北京 100039
  • 3北京大学302临床医学院，北京 100039

    • 王静，硕士研究生，主要从事新冠疫苗免疫应答方面的研究

通讯作者:

王福生，E-mail：
范兴，E-mail：
Characteristics of T cell immune responses in adults inoculated with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months
Jing Wang1, 2, Ya-Qun Li1, 2, Hai-Yan Wang1, 2, Yao-Ru Song2, Jing Li2, 3, Wen-Xin Wang2, 3, Lin-Yu Wan1, 2, Chun-Bao Zhou2, Xing Fan2, * , Fu-Sheng Wang1, 2, *
Affiliations
  • 1The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230001, China
  • 2Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital/National Clinical Research Center for Infectious Diseases, Beijing 100039, China
  • 3Peking University 302 Clinical Medical School, Beijing 100039, China
出版时间: 2024-02-28 doi: 10.11855/j.issn.0577-7402.0075.2023.0427
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摘要
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目的 评估成年人接种新型冠状病毒(SARS-CoV-2)灭活疫苗12个月后不同抗原特异性T细胞免疫应答的特点。方法 解放军总医院第五医学中心2022年4-6月招募15名健康成年人，于接种2剂新冠灭活疫苗12个月后采集其静脉血标本，以基于多色流式细胞术的活化诱导标记法(AIM)检测SARS-CoV-2抗原特异性T淋巴细胞水平，并分析其记忆表型与亚群分化特点。结果 成年人接种2剂灭活疫苗12个月后，90%以上个体可检测到Spike及Non-spike特异性CD4+ T细胞反应(S：14/15，P=0.0001；NS：15/15，P<0.0001)；80%个体检测到Spike及Non-spike特异性CD8+ T细胞反应(S：12/15，P=0.0463；NS：12/15，P=0.0806)。抗原特异性CD4+ T细胞主要表现为中央记忆细胞(CM)、1型效应记忆细胞(EM1)记忆表型，以及1/17型辅助性T细胞(Th1/17)、2型辅助性T细胞(Th2)辅助表型。结论 灭活疫苗接种后能诱导广泛且持久的抗原特异性CD4+ T细胞反应，可能是当前国内新型冠状病毒感染重症化比例较低的关键因素。

新型冠状病毒  /  灭活疫苗  /  T细胞免疫应答

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months. Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine. The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers (AIM) based on polychromatic flow cytometry. Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine, more than 90% of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses (Spike: 14/15, P=0.0001; Non-spike: 15/15, P<0.0001). 80% of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses (Spike: 12/15, P=0.0463; Non-spike: 12/15, P=0.0806). Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory (CM) and effector memory 1 (EM1) cells. On the other hand, in terms of helper subsets, antigen-specific CD4+ T cells mainly showed T helper 1/17 (Th1/17) and T helper 2 (Th2) phenotypes. Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses, which may be the key factor for the low proportion of severe coronavirus disease 2019 (COVID-19) infection in China.

severe acute respiratory syndrome coronavirus 2  /  inactivated vaccine  /  T cell immune response
王静, 李亚群, 汪海燕, 宋曜如, 李静, 王文鑫, 万林钰, 周春保, 范兴, 王福生. 成人接种2剂新冠灭活疫苗12个月后T细胞免疫应答特点. 解放军医学杂志, 2024 , 49 (2) : 165 -170 . DOI: 10.11855/j.issn.0577-7402.0075.2023.0427
Jing Wang, Ya-Qun Li, Hai-Yan Wang, Yao-Ru Song, Jing Li, Wen-Xin Wang, Lin-Yu Wan, Chun-Bao Zhou, Xing Fan, Fu-Sheng Wang. Characteristics of T cell immune responses in adults inoculated with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months[J]. Medical Journal of Chinese People’s Liberation Army, 2024 , 49 (2) : 165 -170 . DOI: 10.11855/j.issn.0577-7402.0075.2023.0427
正文
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新型冠状(新冠)病毒(severe acute respiratory syndrome coronavirus 2，SARS-CoV-2)疫苗是预防新冠病毒感染(coronavirus disease，COVID-19)重症化及死亡的重要手段。截至2022年12月，全球范围内已接种疫苗130亿剂次，其中1/4为灭活病毒疫苗[1]。尽管接种灭活疫苗的人群基数大，但与mRNA疫苗或腺病毒疫苗相比，关于灭活疫苗诱导的细胞免疫反应的研究较少。
当下流行的Omicron毒株逃逸中和抗体的能力强，难以避免突破感染[2]，新冠病毒免疫应答的研究重点开始从保护机体免受感染(主要由抗体介导)转向降低机体感染后疾病重症化的风险(主要由细胞免疫介导)[3-5]。多项研究表明，T细胞在预防疾病严重程度方面发挥着关键作用[6-7]。与体液免疫相比，细胞免疫具有抗原表位保守及衰退速度慢等多方面的优势[8-9]。mRNA疫苗只能诱导S蛋白特异性T细胞反应，灭活疫苗具有N、M、E等其他抗原蛋白，从而能诱导更加广谱的特异性T细胞应答[10-11]。既往关于灭活疫苗T细胞应答的研究主要集中在接种疫苗后的短期效应上，且缺乏对抗原特异性T细胞表型的详细分析[12]。为探究灭活疫苗诱导的SARS-CoV-2特异性T细胞反应的特征及持久性，本研究分析了15名成年个体接种2剂灭活疫苗12个月后外周血中特异性T细胞的水平及表型特点，并探讨了其临床意义。
1 资料与方法
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1.1 一般资料
纳入来自解放军总医院第五医学中心2022年4-6月招募的15名医护人员。纳入标准：(1)年龄≥18岁；(2)接种过2剂新冠灭活疫苗。排除标准：(1)对疫苗成分有过敏反应史；(2)既往有SARS-CoV-2感染史；(3)既往有精神疾病或药物依赖史；(4)不同意参与研究。本研究获得解放军总医院伦理委员会批准(审批号：2020-013-D)。所有受试者在采血前签署书面知情同意书。15名研究对象的中位数年龄为26(23~45)岁；其中男4名，女11名；均无吸烟史、饮酒史及过敏史。所有个体均接种2剂灭活疫苗，其中接种北京科兴灭活疫苗12名，北京生物灭活疫苗3名，2剂疫苗接种间隔28 d[13]，在接种第2剂疫苗351(342~408)d后，收集其外周静脉血，分析抗原特异性T细胞反应。
1.2 方法
1.2.1 外周血标本及淋巴细胞分离
用EDTA-K2采血管(美国BD公司)收集受试者外周静脉血8~10 ml，4 h内分离外周血单个核细胞(peripheral blood mononuclear cells，PBMCs)，室温环境下以2000 r/min离心10 min，吸取上清血浆保存于-80 ℃，下层部分与等体积PBS混匀后均匀铺于Ficoll淋巴细胞分离液上，调整升速及降速至最低档，以2500 r/min离心20 min，吸取白膜层，补加PBS至10 ml，充分混匀后，以2000 r/min离心15 min，洗涤细胞。计数后调整细胞浓度为5×106~1×107 个/ml，加入1 ml细胞冻存液，于液氮中保存备用。
1.2.2 活化诱导标记法(activation-induced markers，AIM)检测SARS-CoV-2特异性T细胞[14]
将1×106个PBMCs细胞置于96孔圆底板中，S组、NS组分别加入5 μg/ml SARS-CoV-2 Spike、Non-spike特异性肽池(附表，江苏南京金斯瑞公司合成)，加入100 μl无血清培养基(美国Thermo公司)，2 h后加入等体积含10%成人血清(北京科霖恩公司)的完全培养基，在37 ℃、5%CO2培养箱中培养24 h。将等摩尔量的二甲基亚砜(DMSO，德国WAK公司)加入DMSO组，作为阴性对照。24 h后收集细胞，加入流式抗体CD14-BV510、CD16-BV510、CD19-BV510、CD56-BV510、CD4-AF700、CD8-PerCP-Cy5.5、CD69-BV421、OX40-PE、CD137-APC、CD45RA-BV605、CD27-PE-Cy7、CXCR3-APC-Cy7、CCR6-BV650、CXCR5-BV711 (美国Biolegend公司)及Fixable Viability Stain 510、CD3-BUV395、CCR7-BUV496(美国BD公司)，混合均匀后于4 ℃孵育0.5 h进行表面染色，PBS洗涤，加入200 μl含1%多聚甲醛的固定液固定细胞，并于24 h内置于FACS Symphony A5型流式细胞仪检测。
1.3 统计学处理
采用GraphPad Prism 9.0.0软件进行统计分析。计数资料以例(%)表示，组间比较采用卡方检验；连续变量以中位数表示，组间比较采用Wilcoxon检验(配对数据)或Mann-Whitney U检验(非配对数据)。P<0.05为差异有统计学意义。
2 结果
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2.1 成年人接种2剂新冠灭活疫苗12个月后T细胞应答水平
接种第2剂疫苗后，与DMSO组相比，大部分个体SARS-CoV-2特异性CD4+ T细胞反应水平升高(S组：14/15，P=0.0001；NS组：15/15，P<0.0001)。S组特异性CD8+ T细胞反应水平比DMSO组略升高(12/15，P=0.0463)，NS组特异性CD8+ T细胞反应水平与DMSO组比较差异无统计学意义(12/15，P=0.0806)，故本研究主要研究CD4+ T细胞免疫应答情况。相较于Spike抗原，Non-spike抗原表位同样也能诱导高水平的特异性CD4+ T细胞反应(P<0.0001，图1)。
2.2 成年人接种2剂新冠灭活疫苗12个月后抗原特异性T细胞记忆表型特征
接种2剂新冠灭活疫苗12个月后，总CD4+ T细胞主要由中央记忆细胞(central memory，CM：CD45RA-CD27+CCR7+)、1型效应记忆细胞(effector memory 1，EM1：CD45RA-CD27+CCR7-)及3型效应记忆细胞(effector memory 3，EM3：CD45RA-CD27-CCR7-)组成。与总CD4+ T细胞相比，抗原特异性CD4+ T细胞中CM表型占比增加(S组：64.5% vs. 32.8%，P=0.0001；NS组：60.6% vs. 32.8%，P<0.0001)，EM3表型占比下降(S组：2.6% vs. 24.4%，P<0.0001；NS组：1.0% vs. 24.4%，P<0.0001)。Spike抗原与Non-spike抗原诱导的抗原特异性T细胞记忆表型差异无统计学意义(P>0.05，图2)。
2.3 成年人接种2剂新冠灭活疫苗12个月后抗原特异性T细胞分化亚群表型特征
接种2剂灭活疫苗12个月后，总CD4+ T细胞主要由滤泡辅助性T细胞(follicular helper T cell，TFH：CXCR5+)、1型辅助性T细胞(T helper 1，Th1：CXCR5-CXCR3+CCR6-)及2型辅助性T细胞(T helper 2，Th2：CXCR5-CXCR3-CCR6-)组成。与总CD4+ T细胞相比，抗原特异性CD4+ T细胞表型主要表现为Th2及1/17型辅助性T细胞(T helper 1/17，Th1/17：CXCR5-CXCR3+CCR6+)表型，TFH及Th1表型CD4+ T细胞比例较低(TFH：S组为8.6% vs. 18.7%，P=0.0006，NS组为5.3% vs. 18.7%，P<0.0001；Th1：S组为3.8% vs. 24.3% ，P<0.0001，NS组为2.1% vs. 24.3%，P<0.0001)。Spike抗原与Non-spike抗原特异性CD4+ T细胞亚群分化表型方面无明显差别(P>0.05，图3)。
3 讨论
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SARS-CoV-2突变株，尤其是Omicron的出现从根本上改变了COVID-19的流行方式及防疫政策的制定。Omicron突变株能够逃避基于武汉原始毒株疫苗诱导的抗体中和能力[3-4]，而细胞免疫成为预防感染重症化的关键[15-16]。本研究发现，成年人接种2剂灭活疫苗12个月后，体内仍能检测到SARS-CoV-2特异性CD4+ T细胞，且Non-spike也可以作为优势抗原引起较强的抗原特异性CD4+ T细胞反应。SARS-CoV-2特异性CD4+ T细胞以CM及EM1记忆表型为主，暗示了其具有较强的维持能力；同时病毒特异性CD4+ T细胞大量富集Th2及Th1/17表型。总之，这些数据证实新冠灭活疫苗能诱导广泛且持久的抗病毒CD4+ T细胞反应，可能是在Omicron毒株大流行的情况下减轻感染者疾病严重程度的关键。
本研究发现，灭活疫苗能够诱导强烈的Spike及Non-spike抗原特异性CD4+ T细胞反应。除SARS-CoV-2病毒Spike之外的抗原蛋白，如N、M、NSP3等，同样能诱导强烈的T细胞反应，是诱导细胞免疫的重要抗原[17]。mRNA疫苗引起的抗原负荷较高，能诱导强烈的体液免疫，但mRNA疫苗是针对Spike蛋白设计的疫苗，只能诱导Spike特异性的T细胞反应[18]。灭活疫苗具有较强的体液免疫效应，而诱导细胞免疫的能力较弱，但其具有SARS-CoV-2的所有抗原蛋白，诱导的T细胞反应更广泛，具有与mRNA疫苗相当的细胞免疫诱导能力[11]。本研究进一步证实了灭活疫苗接种者T细胞反应的广泛性，提示其能在Omicron疫情期间发挥重要的免疫保护作用。
有研究表明，SARS-CoV-2感染康复者及健康个体在mRNA疫苗接种后至少6个月内能维持稳定的细胞免疫水平[9]。接种2剂灭活疫苗4个月后，健康个体体内T细胞免疫反应水平随时间延长而下降，但在感染康复者体内诱导了持久的T细胞反应[19]。本研究探讨了成年人接种2剂灭活疫苗后T细胞免疫反应的持续性，发现灭活疫苗诱导的CD4+ T细胞免疫反应至少能持续12个月，且以CM及EM1记忆表型为主，暗示了其具有很强的持续能力。目前国内正经历Omicron毒株快速传播的时期，但感染者重症化比例及病死率都很低，这可能与灭活疫苗诱导的T细胞免疫反应有关[20-21]。
本研究发现，灭活疫苗诱导的T细胞免疫反应主要是CD4+ T细胞免疫反应。由于抗原递呈方式等方面的差异，灭活疫苗主要诱导CD4+ T细胞免疫反应，而诱导CD8+ T细胞免疫应答的能力较弱[11]。另外，与抗原特异性CD4+ T细胞相比，抗原特异性CD8+ T细胞的衰减速度更快，在接种疫苗6个月后，大部分个体已不能检测到抗原特异性CD8+ T细胞反应[9]。
CD4+ T细胞亚群分化受到TCR信号强弱及微环境中细胞因子的影响[22]。本研究发现，接种疫苗12个月后，抗原特异性CD4+ T细胞以Th2及Th1/17为主。其中，高比例Th2表型抗原特异性CD4+ T细胞的出现，可能是由于随着时间的推移，CD4+ T细胞活化状态的改变以及CXCR5、CCR6、CXCR3等标志物表达下调造成的，CXCR5-CXCR3-CCR6-表型的CD4+ T细胞中只有一部分表达Th2相关效应分子[7,23]。Th1/17表型CD4+ T细胞是一种中间分化态的细胞亚群，能够分泌Th1及Th17亚群相关的细胞因子，可能会通过分泌Th1相关细胞因子，发挥抗病毒免疫反应的作用[24]。抗原特异性CD4+ T细胞中这两个亚群的细胞是否具有相应的功能，仍需要进一步研究。
本研究尚存在一些局限性：一是仅检测了抗原特异性CD4+ T细胞的水平及表型特点，疫苗接种后抗体水平、记忆B细胞水平未研究；二是未排除其他冠状病毒感染，无法除外有交叉反应的个体；三是受试者样本量少，且只随访1次，未能检测到基线及接种疫苗后T细胞水平的动态变化，后续研究中可适当增加随访次数及样本量，以探索T细胞的动态变化。
综上所述，本研究描述了成年人接种2剂灭活疫苗后长期记忆性CD4+ T细胞的水平及表型特点。在Omicron大流行的时期，大量接种灭活疫苗诱导的广泛且持续的CD4+ T细胞反应是免疫保护的关键。本研究为后续基于T细胞免疫应答的新冠病毒疫苗开发提供了新的实验证据。
基金
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  • 广州实验室应急攻关项目(EKPG21-30-4)
文献
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doi: 10.11855/j.issn.0577-7402.0075.2023.0427
  • 接收时间：2023-01-14
  • 首发时间：2025-11-23
  • 出版时间：2024-02-28
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  • 收稿日期：2023-01-14
  • 录用日期：2023-03-08
基金
Guangzhou Laboratory Emergency Response Project(EKPG21-30-4)
广州实验室应急攻关项目(EKPG21-30-4)
作者信息
    1中国科学技术大学附属第一医院，安徽合肥 230001
    2解放军总医院第五医学中心感染病医学部/国家感染性疾病临床医学研究中心，北京 100039
    3北京大学302临床医学院，北京 100039

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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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