tetano
Editor, Senior Moderator
Nat Commun
. 2021 Apr 6;12(1):2055.
doi: 10.1038/s41467-021-21856-3.
T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses
Ane Ogbe[SUP] #[/SUP][SUP] 1 [/SUP], Barbara Kronsteiner[SUP] #[/SUP][SUP] 1 2 [/SUP], Donal T Skelly[SUP] #[/SUP][SUP] 1 3 4 [/SUP], Matthew Pace[SUP] #[/SUP][SUP] 1 [/SUP], Anthony Brown[SUP] #[/SUP][SUP] 1 [/SUP], Emily Adland[SUP] #[/SUP][SUP] 1 [/SUP], Kareena Adair[SUP] 5 [/SUP], Hossain Delowar Akhter[SUP] 1 [/SUP], Mohammad Ali[SUP] 1 2 [/SUP], Serat-E Ali[SUP] 5 [/SUP], Adrienn Angyal[SUP] 6 [/SUP], M Azim Ansari[SUP] 1 [/SUP], Carolina V Arancibia-C?rcamo[SUP] 4 7 [/SUP], Helen Brown[SUP] 1 [/SUP], Senthil Chinnakannan[SUP] 1 [/SUP], Christopher Conlon[SUP] 2 3 [/SUP], Catherine de Lara[SUP] 1 [/SUP], Thushan de Silva[SUP] 6 [/SUP], Christina Dold[SUP] 8 9 [/SUP], Tao Dong[SUP] 10 11 [/SUP], Timothy Donnison[SUP] 1 [/SUP], David Eyre[SUP] 3 12 [/SUP], Amy Flaxman[SUP] 13 [/SUP], Helen Fletcher[SUP] 14 [/SUP], Joshua Gardner[SUP] 5 [/SUP], James T Grist[SUP] 9 15 16 [/SUP], Carl-Philipp Hackstein[SUP] 1 [/SUP], Kanoot Jaruthamsophon[SUP] 5 [/SUP], Katie Jeffery[SUP] 3 [/SUP], Teresa Lambe[SUP] 13 [/SUP], Lian Lee[SUP] 1 [/SUP], Wenqin Li[SUP] 1 [/SUP], Nicholas Lim[SUP] 1 [/SUP], Philippa C Matthews[SUP] 1 3 [/SUP], Alexander J Mentzer[SUP] 3 17 [/SUP], Shona C Moore[SUP] 18 [/SUP], Dean J Naisbitt[SUP] 5 [/SUP], Monday Ogese[SUP] 5 [/SUP], Graham Ogg[SUP] 3 9 10 [/SUP], Peter Openshaw[SUP] 19 [/SUP], Munir Pirmohamed[SUP] 5 [/SUP], Andrew J Pollard[SUP] 8 9 [/SUP], Narayan Ramamurthy[SUP] 1 [/SUP], Patpong Rongkard[SUP] 1 2 20 [/SUP], Sarah Rowland-Jones[SUP] 6 21 [/SUP], Oliver Sampson[SUP] 1 [/SUP], Gavin Screaton[SUP] 17 [/SUP], Alessandro Sette[SUP] 22 23 [/SUP], Lizzie Stafford[SUP] 3 [/SUP], Craig Thompson[SUP] 24 [/SUP], Paul J Thomson[SUP] 5 [/SUP], Ryan Thwaites[SUP] 19 [/SUP], Vinicius Vieira[SUP] 1 25 [/SUP], Daniela Weiskopf[SUP] 22 23 [/SUP], Panagiota Zacharopoulou[SUP] 1 [/SUP], Oxford Immunology Network Covid-19 Response T Cell Consortium; Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team; Lance Turtle[SUP] 18 26 [/SUP], Paul Klenerman[SUP] 27 28 29 30 [/SUP], Philip Goulder[SUP] 25 [/SUP], John Frater[SUP] 1 3 9 [/SUP], Eleanor Barnes[SUP] 1 3 9 [/SUP], Susanna Dunachie[SUP] 1 2 3 9 20 [/SUP]
Collaborators, Affiliations
Abstract
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.
. 2021 Apr 6;12(1):2055.
doi: 10.1038/s41467-021-21856-3.
T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses
Ane Ogbe[SUP] #[/SUP][SUP] 1 [/SUP], Barbara Kronsteiner[SUP] #[/SUP][SUP] 1 2 [/SUP], Donal T Skelly[SUP] #[/SUP][SUP] 1 3 4 [/SUP], Matthew Pace[SUP] #[/SUP][SUP] 1 [/SUP], Anthony Brown[SUP] #[/SUP][SUP] 1 [/SUP], Emily Adland[SUP] #[/SUP][SUP] 1 [/SUP], Kareena Adair[SUP] 5 [/SUP], Hossain Delowar Akhter[SUP] 1 [/SUP], Mohammad Ali[SUP] 1 2 [/SUP], Serat-E Ali[SUP] 5 [/SUP], Adrienn Angyal[SUP] 6 [/SUP], M Azim Ansari[SUP] 1 [/SUP], Carolina V Arancibia-C?rcamo[SUP] 4 7 [/SUP], Helen Brown[SUP] 1 [/SUP], Senthil Chinnakannan[SUP] 1 [/SUP], Christopher Conlon[SUP] 2 3 [/SUP], Catherine de Lara[SUP] 1 [/SUP], Thushan de Silva[SUP] 6 [/SUP], Christina Dold[SUP] 8 9 [/SUP], Tao Dong[SUP] 10 11 [/SUP], Timothy Donnison[SUP] 1 [/SUP], David Eyre[SUP] 3 12 [/SUP], Amy Flaxman[SUP] 13 [/SUP], Helen Fletcher[SUP] 14 [/SUP], Joshua Gardner[SUP] 5 [/SUP], James T Grist[SUP] 9 15 16 [/SUP], Carl-Philipp Hackstein[SUP] 1 [/SUP], Kanoot Jaruthamsophon[SUP] 5 [/SUP], Katie Jeffery[SUP] 3 [/SUP], Teresa Lambe[SUP] 13 [/SUP], Lian Lee[SUP] 1 [/SUP], Wenqin Li[SUP] 1 [/SUP], Nicholas Lim[SUP] 1 [/SUP], Philippa C Matthews[SUP] 1 3 [/SUP], Alexander J Mentzer[SUP] 3 17 [/SUP], Shona C Moore[SUP] 18 [/SUP], Dean J Naisbitt[SUP] 5 [/SUP], Monday Ogese[SUP] 5 [/SUP], Graham Ogg[SUP] 3 9 10 [/SUP], Peter Openshaw[SUP] 19 [/SUP], Munir Pirmohamed[SUP] 5 [/SUP], Andrew J Pollard[SUP] 8 9 [/SUP], Narayan Ramamurthy[SUP] 1 [/SUP], Patpong Rongkard[SUP] 1 2 20 [/SUP], Sarah Rowland-Jones[SUP] 6 21 [/SUP], Oliver Sampson[SUP] 1 [/SUP], Gavin Screaton[SUP] 17 [/SUP], Alessandro Sette[SUP] 22 23 [/SUP], Lizzie Stafford[SUP] 3 [/SUP], Craig Thompson[SUP] 24 [/SUP], Paul J Thomson[SUP] 5 [/SUP], Ryan Thwaites[SUP] 19 [/SUP], Vinicius Vieira[SUP] 1 25 [/SUP], Daniela Weiskopf[SUP] 22 23 [/SUP], Panagiota Zacharopoulou[SUP] 1 [/SUP], Oxford Immunology Network Covid-19 Response T Cell Consortium; Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team; Lance Turtle[SUP] 18 26 [/SUP], Paul Klenerman[SUP] 27 28 29 30 [/SUP], Philip Goulder[SUP] 25 [/SUP], John Frater[SUP] 1 3 9 [/SUP], Eleanor Barnes[SUP] 1 3 9 [/SUP], Susanna Dunachie[SUP] 1 2 3 9 20 [/SUP]
Collaborators, Affiliations
- PMID: 33824342
- DOI: 10.1038/s41467-021-21856-3
Abstract
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.