Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.
Authors
Diniz, Mariana O
Amin, Oliver E
Chandran, Aneesh
Shaw, Emily
Pade, Corinna
Tan, Anthony T
Jeffery-Smith, Anna
Tan, Cedric CS
Aidoo-Micah, Gloryanne
Davies, Jessica
Johnson, Marina
Jensen, Melanie P
Joy, George
Altmann, Daniel M
Manisty, Charlotte
Treibel, Thomas A
Moon, James C
COVIDsortium Investigators
McKnight, Áine
Publication Date
2022-01Journal Title
Nature
ISSN
0028-0836
Publisher
Springer Science and Business Media LLC
Volume
601
Issue
7891
Pages
110-117
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Swadling, L., Diniz, M. O., Schmidt, N. M., Amin, O. E., Chandran, A., Shaw, E., Pade, C., et al. (2022). Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.. Nature, 601 (7891), 110-117. https://doi.org/10.1038/s41586-021-04186-8
Abstract
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 infections1-3. 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.
Keywords
Article, /631/250/2152/1566/1571, /631/250/254, /631/250/1619/554, /631/326/596/4130, /13/1, /13/31, /13/106, /82/75, article
Identifiers
s41586-021-04186-8, 4186
External DOI: https://doi.org/10.1038/s41586-021-04186-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333055
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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