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@article{Swadling:2021:10.1038/s41586-021-04186-8,
author = {Swadling, L and Diniz, MO and Schmidt, NM and Amin, OE and Chandran, A and Shaw, E and Pade, C and Gibbons, JM and Le, Bert N and Tan, AT and Jeffery-Smith, A and Tan, CCS and Tham, CYL and Kucykowicz, S and Aidoo-Micah, G and Rosenheim, J and Davies, J and Johnson, M and Jensen, MP and Joy, G and McCoy, LE and Valdes, AM and Chain, BM and Goldblatt, D and Altmann, DM and Boyton, RJ and Manisty, C and Treibel, TA and Moon, JC and COVIDsortium, investigators and Dorp, LV and Balloux, F and McKnight, Á and Noursadeghi, M and Bertoletti, A and Maini, MK},
doi = {10.1038/s41586-021-04186-8},
journal = {Nature},
pages = {110--117},
title = {Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2},
url = {http://dx.doi.org/10.1038/s41586-021-04186-8},
volume = {601},
year = {2021}
}

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TY  - JOUR
AB  - 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 infections1-3. 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-CoV-2-reactive T-cells, including those against the early transcribed replication transcription complex (RTC)12,13, 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-214, 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.
AU  - Swadling,L
AU  - Diniz,MO
AU  - Schmidt,NM
AU  - Amin,OE
AU  - Chandran,A
AU  - Shaw,E
AU  - Pade,C
AU  - Gibbons,JM
AU  - Le,Bert N
AU  - Tan,AT
AU  - Jeffery-Smith,A
AU  - Tan,CCS
AU  - Tham,CYL
AU  - Kucykowicz,S
AU  - Aidoo-Micah,G
AU  - Rosenheim,J
AU  - Davies,J
AU  - Johnson,M
AU  - Jensen,MP
AU  - Joy,G
AU  - McCoy,LE
AU  - Valdes,AM
AU  - Chain,BM
AU  - Goldblatt,D
AU  - Altmann,DM
AU  - Boyton,RJ
AU  - Manisty,C
AU  - Treibel,TA
AU  - Moon,JC
AU  - COVIDsortium,investigators
AU  - Dorp,LV
AU  - Balloux,F
AU  - McKnight,Á
AU  - Noursadeghi,M
AU  - Bertoletti,A
AU  - Maini,MK
DO  - 10.1038/s41586-021-04186-8
EP  - 117
PY  - 2021///
SN  - 0028-0836
SP  - 110
TI  - Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-021-04186-8
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34758478
UR  - https://www.nature.com/articles/s41586-021-04186-8
UR  - http://hdl.handle.net/10044/1/92688
VL  - 601
ER  -

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