Details

Autor(en) / Beteiligte

• Swadling, Leo
• Diniz, Mariana O.
• Schmidt, Nathalie M.
• Amin, Oliver E.
• Chandran, Aneesh
• Shaw, Emily
• Pade, Corinna
• Gibbons, Joseph M.
• Le Bert, Nina
• Tan, Anthony T.
• Jeffery-Smith, Anna
• Tan, Cedric C. S.
• Tham, Christine Y. L.
• Kucykowicz, Stephanie
• Aidoo-Micah, Gloryanne
• Rosenheim, Joshua
• Davies, Jessica
• Johnson, Marina
• Jensen, Melanie P.
• Joy, George
• McCoy, Laura E.
• Valdes, Ana M.
• Chain, Benjamin M.
• Goldblatt, David
• Altmann, Daniel M.
• Boyton, Rosemary J.
• Manisty, Charlotte
• Treibel, Thomas A.
• Moon, James C.
• van Dorp, Lucy
• Balloux, Francois
• McKnight, Áine
• Noursadeghi, Mahdad
• Bertoletti, Antonio
• Maini, Mala K.

Titel

Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2

Ist Teil von

• Nature (London), 2022-01, Vol.601 (7891), p.110-117

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections 1 – 3 . Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4 – 11 ), 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) 12 , 13 , in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27 , a robust early innate signature of SARS-CoV-2 (ref. 14 ), 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 (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. 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 . Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.