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

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., and others. (2021) Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature, . ISSN 0028-0836. (doi:10.1038/s41586-021-04186-8) (KAR id:91508)

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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. We hypothesised that pre-existing memory T-cell responses, with cross-protective potential against SARS-CoV-24–11, would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV2-reactive T-cells, including those against the early transcribed replication transcription complex (RTC), 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, 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.

Item Type: Article
DOI/Identification number: 10.1038/s41586-021-04186-8
Uncontrolled keywords: Immunological memory, Infection, SARS-CoV-2, T cells, COVID-19
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 10 Nov 2021 22:19 UTC
Last Modified: 11 Nov 2021 10:32 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/91508 (The current URI for this page, for reference purposes)
Temperton, Nigel J.: https://orcid.org/0000-0002-7978-3815
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