T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
;
Barbara Kronsteiner;
Donal T Skelly ;
Matthew Pace;
Anthony Brown ;
Emily Adland;
Kareena Adair;
Hossain Delowar Akhter;
Mohammad Ali ;
Serat-E Ali;
+53 more...
Adrienn Angyal;
M Azim Ansari;
Carolina V Arancibia-Cárcamo;
Helen Brown;
Senthil Chinnakannan ;
Christopher Conlon ;
Catherine de Lara;
Thushan de Silva;
Christina Dold;
Tao Dong;
Timothy Donnison ;
David Eyre;
Amy Flaxman ;
Helen Fletcher ;
Joshua Gardner;
James T Grist;
Carl-Philipp Hackstein;
Kanoot Jaruthamsophon ;
Katie Jeffery ;
Teresa Lambe ;
Lian Lee ;
Wenqin Li;
Nicholas Lim;
Philippa C Matthews ;
Alexander J Mentzer ;
Shona C Moore ;
Dean J Naisbitt;
Monday Ogese;
Graham Ogg;
Peter Openshaw ;
Munir Pirmohamed;
Andrew J Pollard ;
Narayan Ramamurthy;
Patpong Rongkard;
Sarah Rowland-Jones;
Oliver Sampson ;
Gavin Screaton;
Alessandro Sette;
Lizzie Stafford;
Craig Thompson ;
Paul J Thomson;
Ryan Thwaites ;
Vinicius Vieira ;
Daniela Weiskopf;
Panagiota Zacharopoulou;
Oxford Immunology Network Covid-19 Response T Cell Consortium;
Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinica;
Lance Turtle ;
Paul Klenerman ;
Philip Goulder;
John Frater ;
Eleanor Barnes ;
Susanna Dunachie ;
Oxford Immunology Network Covid-19 Response T Cell Consortium, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinica;
(2021)
T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.
Nature communications, 12 (1).
2055-.
ISSN 2041-1723
DOI: 10.1038/s41467-021-21856-3
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.
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