SARS-CoV-2 breakthrough infection in vaccinees induces virus-specific nasal-resident CD8+ and CD4+ T cells of broad specificity

  1. Joey Ming Er Lim
  2. Anthony Tanoto Tan
  3. Nina Le Bert
  4. Shou Kit Hang
  5. Jenny Guek Hong Low
  6. Antonio Bertoletti

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Abstract

Rapid recognition of SARS-CoV-2–infected cells by resident T cells in the upper airway might provide an important layer of protection against COVID-19. Whether parenteral SARS-CoV-2 vaccination or infection induces nasal-resident T cells specific for distinct SARS-CoV-2 proteins is unknown. We isolated T cells from the nasal mucosa of COVID-19 vaccinees who either experienced SARS-CoV-2 infection after vaccination (n = 34) or not (n = 16) and analyzed their phenotype, SARS-CoV-2 specificity, function, and persistence. Nasal-resident SARS-CoV-2–specific CD8+ and CD4+ T cells were detected almost exclusively in vaccinees who experienced SARS-CoV-2 breakthrough infection. Importantly, the Spike-specific T cells primed by vaccination did not suppress the induction of T cells specific for other SARS-CoV-2 proteins. The nasal-resident T cell responses persisted for ≥140 d, with minimal sign of waning. These data highlight the importance of viral nasal challenge in the formation of SARS-CoV-2–specific antiviral immunity at the site of primary infection and further define the immunological features of SARS-CoV-2 hybrid immunity.

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  1. Version published to 10.1084/jem.20220780
  2. ScreenIT

    SciScore for 10.1101/2022.05.18.22275292: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Study participants: This study was approved by the SingHealth Centralized Institutional Review Board (CIRB/F 2021/2014).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are limitations in this study; in addition to the small sample size, phenotypic analysis of the nasal T cells and analysis of their SARS-CoV-2 specificity was limited to few markers of tissue residency (CD69 and CD103) and memory (CD45RA and CCR7) and to selected SARS-CoV-2 proteins (NP, membrane, Spike and NSP-12). The limited number of T cells collected impose these limitations. To better define the breath of the nasal resident T cell response against SARS-CoV-2 it will be necessary to analyze their ability to recognize epitopes derived from others structural, non-structural proteins or out-of-frame Open Reading Frames that have been shown to induce robust CD8 T cell response in circulation(Weingarten-Gabbay et al., 2021). The potential distinct functionality of Nasal SARS-CoV-2 T cells will need also to be analyzed by analysis of their transcriptomic profile, in addition their ability to produce IFN-γ and degranulate. Finally, as already mentioned, study of the durability of the nasal resident SARS-CoV-2 T cells over 3 months are warranted to understand the long-term impact of nasal resident T cells in SARS-CoV-2 protection.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2022.05.18.22275292v1 on medRxiv