T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
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DOI：
10.1038/s41467-021-21856-3
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发表时间：
2021-04-06
影响因子：
16.6
通讯作者：
Dunachie S
中科院分区：
文献类型：
--
作者：
Ogbe A;Kronsteiner B;Skelly DT;Pace M;Brown A;Adland E;Adair K;Akhter HD;Ali M;Ali SE;Angyal A;Ansari MA;Arancibia-Cárcamo CV;Brown H;Chinnakannan S;Conlon C;de Lara C;de Silva T;Dold C;Dong T;Donnison T;Eyre D;Flaxman A;Fletcher H;Gardner J;Grist JT;Hackstein CP;Jaruthamsophon K;Jeffery K;Lambe T;Lee L;Li W;Lim N;Matthews PC;Mentzer AJ;Moore SC;Naisbitt DJ;Ogese M;Ogg G;Openshaw P;Pirmohamed M;Pollard AJ;Ramamurthy N;Rongkard P;Rowland-Jones S;Sampson O;Screaton G;Sette A;Stafford L;Thompson C;Thomson PJ;Thwaites R;Vieira V;Weiskopf D;Zacharopoulou P;Oxford Immunology Network Covid-19 Response T Cell Consortium;Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team;Turtle L;Klenerman P;Goulder P;Frater J;Barnes E;Dunachie S
鉴定针对SARS-CoV-2的保护性T细胞反应需要将SARS-CoV-2感染者与对其他冠状病毒具有交叉反应性免疫的人区分开来。在这里，我们展示了一系列T细胞检测，这些检测以不同的方式捕获免疫功能，以表征SARS-CoV-2反应。在168例pcr确诊的SARS-CoV-2感染志愿者中发现了较强的体外ELISpot和对多种抗原（包括M、NP和ORF3）的增殖反应，但在119例未感染志愿者中却罕见。最近患有covid -19相容疾病的高度暴露血清阴性卫生保健工作者显示出感染特征的T细胞反应模式。相比之下，b> 90%的恢复期或未暴露的人表现出对刺突亚基S1/S2的增殖和细胞乳酸反应，表明存在交叉反应性T细胞群。因此，检测T细胞对SARS-CoV-2的反应严重依赖于检测和抗原选择。对特定非刺突蛋白的记忆反应提供了一种在暴露人群中区分近期感染和先前免疫的方法。了解对SARS-CoV-2的免疫反应取决于能够区分COVID-19免疫反应与对其他冠状病毒的交叉反应性免疫反应。在这里，作者表明抗原的选择以及是否使用ICS、ELISPOT或T细胞增殖试验对这种区分能力有主要影响。
Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations. Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.
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影响因子：
17.1
作者：
Swadling L;Capone S;Antrobus RD;Brown A;Richardson R;Newell EW;Halliday J;Kelly C;Bowen D;Fergusson J;Kurioka A;Ammendola V;Del Sorbo M;Grazioli F;Esposito ML;Siani L;Traboni C;Hill A;Colloca S;Davis M;Nicosia A;Cortese R;Folgori A;Klenerman P;Barnes E
通讯作者：
Barnes E
影响因子：
--
作者：
Severance, Emily G.;Bossis, Ioannis;Viscidi, Raphael P.
通讯作者：
Viscidi, Raphael P.
影响因子：
3.7
作者：
Lee, Jamie A.;Spidlen, Josef;Boyce, Keith;Cai, Jennifer;Crosbie, Nicholas;Dalphin, Mark;Furlong, Jeff;Gasparetto, Maura.;Goldberg, Michael;Goralczyk, Elizabeth M.;Hyun, Bill;Jansen, Kirstin;Kollmann, Tobias;Kong, Megan;Leif, Robert;McWeeney, Shannon;Moloshok, Thomas D.;Moore, Wayne;Nolan, Garry;Nolan, John;Nikolich-Zugich, Janko;Parrish, David;Purcell, Barclay;Qian, Yu;Selvaraj, Biruntha;Smith, Clayton;Tchuvatkina, Olga;Wertheimer, Anne;WilkinSon, Peter;Wilson, Christopher;Wood, James;Zigon, Robert;Scheuermann, Richard H.;Brinkman, Ryan R.
通讯作者：
Brinkman, Ryan R.
影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F