Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.
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DOI：
10.1038/s41586-021-04186-8
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发表时间：
2022-01
期刊：
影响因子：
64.8
通讯作者：
Maini MK
中科院分区：
文献类型：
--
作者：
Swadling L;Diniz MO;Schmidt NM;Amin OE;Chandran A;Shaw E;Pade C;Gibbons JM;Le Bert N;Tan AT;Jeffery-Smith A;Tan CCS;Tham CYL;Kucykowicz S;Aidoo-Micah G;Rosenheim J;Davies J;Johnson M;Jensen MP;Joy G;McCoy LE;Valdes AM;Chain BM;Goldblatt D;Altmann DM;Boyton RJ;Manisty C;Treibel TA;Moon JC;COVIDsortium Investigators;van Dorp L;Balloux F;McKnight Á;Noursadeghi M;Bertoletti A;Maini MK
可能接触严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的人不一定会出现聚合酶链式反应或抗体阳性，这表明一些人可能在血清转换之前清除了亚临床感染。T细胞有助于迅速清除SARS-CoV-2和其他冠状病毒感染。在这里，我们假设先前存在的记忆T细胞反应，具有对抗SARS-CoV-2的交叉保护潜力(参考文献。)，将在体内扩大，以支持快速病毒控制，流产感染。我们检测了SARS-CoV-2反应性T细胞，包括针对早期转录复制-转录复合体(RTC)的T细胞，这些T细胞根据聚合酶链式反应(PCR)、抗体结合和中和试验(血清阴性的HCW)反复检测呈阴性的密切监测的医护人员(HCW)。与大流行前的一组未暴露的人相比，SN-HW有更强的、更多特异性的记忆T细胞(流行前队列)，这些细胞更频繁地针对RTC，而不是在可检测到的感染后观察到的以结构蛋白为主的反应(匹配的并发队列)。具有最强RTC特异性T细胞的SN-HCW有IFI27的增加，IFI27是SARS-CoV-2的一个强大的早期先天特征(参考。)，表明是流产感染。RTC中的RNA聚合酶是人类季节性冠状病毒(HCoV)和SARS-CoV-2分支之间最大的高序列保守区。RNA聚合酶优先被来自流行前期队列和SN-HW的T细胞靶向(在被测试的区域中)。在SN-HWs中发现了交叉识别HCoV变异体的RTC表位特异性T细胞。与明显的SARS-CoV-2感染相比，丰富的预先存在的RNA聚合酶特异性T细胞在体内扩增，在假定流产后优先在记忆反应中积累。我们的数据强调RTC特异性T细胞是针对地方性和新兴冠状病毒科的疫苗的靶标。具有先天感染特征的血清阴性医护人员在流产感染中优先针对SARS-CoV-2保守的复制转录复合体扩大先前存在的T细胞。
Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections. Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. ), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication–transcription complex (RTC), in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2 (ref. ), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae. Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.
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影响因子：
11.8
作者：
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30.3
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