tetano
Editor, Senior Moderator
JCI Insight
. 2022 May 24;e156372.
doi: 10.1172/jci.insight.156372. Online ahead of print.
Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
Anna L McNaughton[SUP] 1 [/SUP], Robert S Paton[SUP] 2 [/SUP], Matthew Edmans[SUP] 1 [/SUP], Jonathan Cw Youngs[SUP] 3 [/SUP], Judith Wellens[SUP] 1 [/SUP], Prabhjeet Phalora[SUP] 1 [/SUP], Alex Fyfe[SUP] 2 [/SUP], Sandra Belij-Rammerstorfer[SUP] 4 [/SUP], Jai S Bolton[SUP] 2 [/SUP], Jonathan Ball[SUP] 5 [/SUP], George W Carnell[SUP] 6 [/SUP], Wanwisa Dejnirattisai[SUP] 1 [/SUP], Christina Dold[SUP] 7 [/SUP], David W Eyre[SUP] 8 [/SUP], Philip Hopkins[SUP] 9 [/SUP], Alison Howarth[SUP] 10 [/SUP], Kreepa Kooblall[SUP] 11 [/SUP], Hannah Klim[SUP] 2 [/SUP], Susannah Leaver[SUP] 12 [/SUP], Lian N Lee[SUP] 1 [/SUP], César López-Camacho[SUP] 1 [/SUP], Sheila F Lumley[SUP] 1 [/SUP], Derek C Macallan[SUP] 13 [/SUP], Alexander J Mentzer[SUP] 14 [/SUP], Nicholas M Provine[SUP] 15 [/SUP], Jeremy Ratcliff[SUP] 1 [/SUP], Jose L Slon-Campos[SUP] 1 [/SUP], Donal T Skelly[SUP] 16 [/SUP], Lucas B Stolle[SUP] 17 [/SUP], Piyada Supasa[SUP] 1 [/SUP], Nigel Temperton[SUP] 18 [/SUP], Chris Walker[SUP] 19 [/SUP], Beibei Wang[SUP] 1 [/SUP], Duncan Wyncoll[SUP] 20 [/SUP], Peter Simmonds[SUP] 1 [/SUP], Teresa Lambe[SUP] 4 [/SUP], John K Ballie[SUP] 21 [/SUP], Malcolm G Semple[SUP] 22 [/SUP], Peter Jm Openshaw[SUP] 23 [/SUP], Uri Obolski[SUP] 24 [/SUP], Marc Turner[SUP] 25 [/SUP], Miles Carroll[SUP] 26 [/SUP], Juthathip Mongkolsapaya[SUP] 1 [/SUP], Gavin Screaton[SUP] 1 [/SUP], Stephen H Kennedy[SUP] 27 [/SUP], Lisa M Jarvis[SUP] 25 [/SUP], Eleanor Barnes[SUP] 28 [/SUP], Susanna Dunachie[SUP] 1 [/SUP], José Lourenço[SUP] 2 [/SUP], Philippa C Matthews[SUP] 29 [/SUP], Tihana Bicanic[SUP] 30 [/SUP], Paul Klenerman[SUP] 28 [/SUP], Sunetra Gupta[SUP] 2 [/SUP], Craig P Thompson[SUP] 2 [/SUP]
Affiliations
Abstract
The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.
Keywords: Adaptive immunity; Immunology; Imprinting; Infectious disease.
. 2022 May 24;e156372.
doi: 10.1172/jci.insight.156372. Online ahead of print.
Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
Anna L McNaughton[SUP] 1 [/SUP], Robert S Paton[SUP] 2 [/SUP], Matthew Edmans[SUP] 1 [/SUP], Jonathan Cw Youngs[SUP] 3 [/SUP], Judith Wellens[SUP] 1 [/SUP], Prabhjeet Phalora[SUP] 1 [/SUP], Alex Fyfe[SUP] 2 [/SUP], Sandra Belij-Rammerstorfer[SUP] 4 [/SUP], Jai S Bolton[SUP] 2 [/SUP], Jonathan Ball[SUP] 5 [/SUP], George W Carnell[SUP] 6 [/SUP], Wanwisa Dejnirattisai[SUP] 1 [/SUP], Christina Dold[SUP] 7 [/SUP], David W Eyre[SUP] 8 [/SUP], Philip Hopkins[SUP] 9 [/SUP], Alison Howarth[SUP] 10 [/SUP], Kreepa Kooblall[SUP] 11 [/SUP], Hannah Klim[SUP] 2 [/SUP], Susannah Leaver[SUP] 12 [/SUP], Lian N Lee[SUP] 1 [/SUP], César López-Camacho[SUP] 1 [/SUP], Sheila F Lumley[SUP] 1 [/SUP], Derek C Macallan[SUP] 13 [/SUP], Alexander J Mentzer[SUP] 14 [/SUP], Nicholas M Provine[SUP] 15 [/SUP], Jeremy Ratcliff[SUP] 1 [/SUP], Jose L Slon-Campos[SUP] 1 [/SUP], Donal T Skelly[SUP] 16 [/SUP], Lucas B Stolle[SUP] 17 [/SUP], Piyada Supasa[SUP] 1 [/SUP], Nigel Temperton[SUP] 18 [/SUP], Chris Walker[SUP] 19 [/SUP], Beibei Wang[SUP] 1 [/SUP], Duncan Wyncoll[SUP] 20 [/SUP], Peter Simmonds[SUP] 1 [/SUP], Teresa Lambe[SUP] 4 [/SUP], John K Ballie[SUP] 21 [/SUP], Malcolm G Semple[SUP] 22 [/SUP], Peter Jm Openshaw[SUP] 23 [/SUP], Uri Obolski[SUP] 24 [/SUP], Marc Turner[SUP] 25 [/SUP], Miles Carroll[SUP] 26 [/SUP], Juthathip Mongkolsapaya[SUP] 1 [/SUP], Gavin Screaton[SUP] 1 [/SUP], Stephen H Kennedy[SUP] 27 [/SUP], Lisa M Jarvis[SUP] 25 [/SUP], Eleanor Barnes[SUP] 28 [/SUP], Susanna Dunachie[SUP] 1 [/SUP], José Lourenço[SUP] 2 [/SUP], Philippa C Matthews[SUP] 29 [/SUP], Tihana Bicanic[SUP] 30 [/SUP], Paul Klenerman[SUP] 28 [/SUP], Sunetra Gupta[SUP] 2 [/SUP], Craig P Thompson[SUP] 2 [/SUP]
Affiliations
- PMID: 35608920
- DOI: 10.1172/jci.insight.156372
Abstract
The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.
Keywords: Adaptive immunity; Immunology; Imprinting; Infectious disease.