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Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2, 2021, Leo Swadling et al

Discussion in 'Epidemics (including Covid-19, not Long Covid)' started by Sean, Dec 8, 2021.

  1. Sean

    Sean Senior Member (Voting Rights)

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

    Leo Swadling, et al.

    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.

    https://pubmed.ncbi.nlm.nih.gov/34758478/
     
  2. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    How did they control for the level of exposure 'dosage'?

    The abortive infection could be in part due to a lower quantity of virus exposure in the first place - so a few T-cells could clean up the mess easily, whereas with a higher exposure dose that might not be possible.
     

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