tetano
Editor, Senior Moderator
Nature
. 2021 Nov 10.
doi: 10.1038/s41586-021-04186-8. Online ahead of print.
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
Leo Swadling[SUP] 1 [/SUP], Mariana O Diniz[SUP] #[/SUP][SUP] 2 [/SUP], Nathalie M Schmidt[SUP] #[/SUP][SUP] 2 [/SUP], Oliver E Amin[SUP] #[/SUP][SUP] 2 [/SUP], Aneesh Chandran[SUP] #[/SUP][SUP] 2 [/SUP], Emily Shaw[SUP] #[/SUP][SUP] 2 [/SUP], Corinna Pade[SUP] 3 [/SUP], Joseph M Gibbons[SUP] 3 [/SUP], Nina Le Bert[SUP] 4 [/SUP], Anthony T Tan[SUP] 4 [/SUP], Anna Jeffery-Smith[SUP] 2 3 [/SUP], Cedric C S Tan[SUP] 5 [/SUP], Christine Y L Tham[SUP] 4 [/SUP], Stephanie Kucykowicz[SUP] 2 [/SUP], Gloryanne Aidoo-Micah[SUP] 2 [/SUP], Joshua Rosenheim[SUP] 2 [/SUP], Jessica Davies[SUP] 2 [/SUP], Marina Johnson[SUP] 6 [/SUP], Melanie P Jensen[SUP] 7 8 [/SUP], George Joy[SUP] 7 9 [/SUP], Laura E McCoy[SUP] 2 [/SUP], Ana M Valdes[SUP] 10 11 [/SUP], Benjamin M Chain[SUP] 2 [/SUP], David Goldblatt[SUP] 6 [/SUP], Daniel M Altmann[SUP] 12 [/SUP], Rosemary J Boyton[SUP] 13 14 [/SUP], Charlotte Manisty[SUP] 7 9 [/SUP], Thomas A Treibel[SUP] 7 9 [/SUP], James C Moon[SUP] 7 9 [/SUP], COVIDsortium investigators; Lucy van Dorp[SUP] 5 [/SUP], Francois Balloux[SUP] 5 [/SUP], Áine McKnight[SUP] 3 [/SUP], Mahdad Noursadeghi[SUP] #[/SUP][SUP] 2 [/SUP], Antonio Bertoletti[SUP] #[/SUP][SUP] 4 15 [/SUP], Mala K Maini[SUP] 16 [/SUP]
Collaborators, Affiliations
Abstract
Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T-cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections[SUP]1-3[/SUP]. We hypothesised that pre-existing memory T-cell responses, with cross-protective potential against SARS-CoV-2[SUP]4-11[/SUP], 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)[SUP]12,13[/SUP], in intensively monitored healthcare workers (HCW) remaining repeatedly negative by PCR, antibody binding, and neutralisation (seronegative HCW, SN-HCW). SN-HCW had stronger, more multispecific memory T-cells than an unexposed pre-pandemic cohort, and more frequently directed against the RTC than the structural protein-dominated responses seen post-detectable infection (matched concurrent cohort). SN-HCW with the strongest RTC-specific T-cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2[SUP]14[/SUP], 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 (amongst regions tested) by T-cells from pre-pandemic cohorts and SN-HCW. RTC epitope-specific T-cells cross-recognising HCoV variants were identified in SN-HCW. 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.
. 2021 Nov 10.
doi: 10.1038/s41586-021-04186-8. Online ahead of print.
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
Leo Swadling[SUP] 1 [/SUP], Mariana O Diniz[SUP] #[/SUP][SUP] 2 [/SUP], Nathalie M Schmidt[SUP] #[/SUP][SUP] 2 [/SUP], Oliver E Amin[SUP] #[/SUP][SUP] 2 [/SUP], Aneesh Chandran[SUP] #[/SUP][SUP] 2 [/SUP], Emily Shaw[SUP] #[/SUP][SUP] 2 [/SUP], Corinna Pade[SUP] 3 [/SUP], Joseph M Gibbons[SUP] 3 [/SUP], Nina Le Bert[SUP] 4 [/SUP], Anthony T Tan[SUP] 4 [/SUP], Anna Jeffery-Smith[SUP] 2 3 [/SUP], Cedric C S Tan[SUP] 5 [/SUP], Christine Y L Tham[SUP] 4 [/SUP], Stephanie Kucykowicz[SUP] 2 [/SUP], Gloryanne Aidoo-Micah[SUP] 2 [/SUP], Joshua Rosenheim[SUP] 2 [/SUP], Jessica Davies[SUP] 2 [/SUP], Marina Johnson[SUP] 6 [/SUP], Melanie P Jensen[SUP] 7 8 [/SUP], George Joy[SUP] 7 9 [/SUP], Laura E McCoy[SUP] 2 [/SUP], Ana M Valdes[SUP] 10 11 [/SUP], Benjamin M Chain[SUP] 2 [/SUP], David Goldblatt[SUP] 6 [/SUP], Daniel M Altmann[SUP] 12 [/SUP], Rosemary J Boyton[SUP] 13 14 [/SUP], Charlotte Manisty[SUP] 7 9 [/SUP], Thomas A Treibel[SUP] 7 9 [/SUP], James C Moon[SUP] 7 9 [/SUP], COVIDsortium investigators; Lucy van Dorp[SUP] 5 [/SUP], Francois Balloux[SUP] 5 [/SUP], Áine McKnight[SUP] 3 [/SUP], Mahdad Noursadeghi[SUP] #[/SUP][SUP] 2 [/SUP], Antonio Bertoletti[SUP] #[/SUP][SUP] 4 15 [/SUP], Mala K Maini[SUP] 16 [/SUP]
Collaborators, Affiliations
- PMID: 34758478
- DOI: 10.1038/s41586-021-04186-8
Abstract
Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T-cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections[SUP]1-3[/SUP]. We hypothesised that pre-existing memory T-cell responses, with cross-protective potential against SARS-CoV-2[SUP]4-11[/SUP], 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)[SUP]12,13[/SUP], in intensively monitored healthcare workers (HCW) remaining repeatedly negative by PCR, antibody binding, and neutralisation (seronegative HCW, SN-HCW). SN-HCW had stronger, more multispecific memory T-cells than an unexposed pre-pandemic cohort, and more frequently directed against the RTC than the structural protein-dominated responses seen post-detectable infection (matched concurrent cohort). SN-HCW with the strongest RTC-specific T-cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2[SUP]14[/SUP], 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 (amongst regions tested) by T-cells from pre-pandemic cohorts and SN-HCW. RTC epitope-specific T-cells cross-recognising HCoV variants were identified in SN-HCW. 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.