T cell responses to SARS-CoV-2 spike cross-recognize Omicron

  1. Roanne Keeton
  2. Marius B. Tincho
  3. Amkele Ngomti
  4. Richard Baguma
  5. Ntombi Benede
  6. Akiko Suzuki
  7. Khadija Khan
  8. Sandile Cele
  9. Mallory Bernstein
  10. Farina Karim
  11. Sharon V. Madzorera
  12. Thandeka Moyo-Gwete
  13. Mathilda Mennen
  14. Sango Skelem
  15. Marguerite Adriaanse
  16. Daniel Mutithu
  17. Olukayode Aremu
  18. Cari Stek
  19. Elsa du Bruyn
  20. Mieke A. Van Der Mescht
  21. Zelda de Beer
  22. Talita R. de Villiers
  23. Annie Bodenstein
  24. Gretha van den Berg
  25. Adriano Mendes
  26. Amy Strydom
  27. Marietjie Venter
  28. Jennifer Giandhari
  29. Yeshnee Naidoo
  30. Sureshnee Pillay
  31. Houriiyah Tegally
  32. Alba Grifoni
  33. Daniela Weiskopf
  34. Alessandro Sette
  35. Robert J. Wilkinson
  36. Tulio de Oliveira
  37. Linda-Gail Bekker
  38. Glenda Gray
  39. Veronica Ueckermann
  40. Theresa Rossouw
  41. Michael T. Boswell
  42. Jinal N. Bhiman
  43. Penny L. Moore
  44. Alex Sigal
  45. Ntobeko A. B. Ntusi
  46. Wendy A. Burgers
  47. Catherine Riou

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Abstract

The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations 1,2 that contribute to viral escape from antibody neutralization 3–6 and reduce vaccine protection from infection 7,8 . The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients ( n  = 70). Between 70% and 80% of the CD4 + and CD8 + T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections ( n  = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants ( n  = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere 9–12 .

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  1. Version published to 10.1038/s41586-022-04460-3
  2. ScreenIT

    SciScore for 10.1101/2021.12.26.21268380: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the University of Cape Town Human Research Ethics Committee (ref: HREC 190/2020, 207/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (ref.
    Consent: Written informed consent was obtained from all participants.
    Field Sample Permit: Isolation of PBMC: Blood was collected in heparin tubes and processed within 4 hours of collection.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    All stimulations were performed in the presence of Brefeldin A (10 µg/mL, Sigma-Aldrich, St Louis, MO, USA) and co-stimulatory antibodies against CD28 (clone 28.2) and CD49d (clone L25) (1 µg/mL each; BD Biosciences, San Jose, CA, USA).
    CD28
    suggested: (BD Biosciences Cat# 347690, RRID:AB_647457)
    CD49d
    suggested: None
    Cells were infected with 100 μL of the virus–antibody mixtures for 1 h, then 100 μL of a 1X RPMI 1640 (Sigma-Aldrich, R6504), 1.5% carboxymethylcellulose (Sigma-Aldrich, C4888) overlay was added without removing the inoculum.
    R6504
    suggested: (Fitzgerald Industries International Cat# 10R-6504, RRID:AB_11190346)
    Foci were stained with a rabbit anti-spike monoclonal antibody (BS-R2B12, GenScript A02058) at 0.5 μg/mL in a permeabilization buffer containing 0.1% saponin (Sigma-Aldrich), 0.1% BSA (Sigma-Aldrich) and 0.05% Tween-20 (Sigma-Aldrich) in PBS.
    anti-spike
    suggested: None
    Secondary goat anti-rabbit horseradish peroxidase (Abcam ab205718) antibody was added at 1 μg/mL and incubated for 2 h at room temperature with shaking.
    anti-rabbit
    suggested: (Abcam Cat# ab205718, RRID:AB_2819160)
    CB6 and CA1 monoclonal antibodies were used as controls.
    CB6
    suggested: None
    CA1
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    H1299-E3 cells were plated in a 96-well plate (Corning) at 30,000 cells per well 1 day pre-infection.
    H1299-E3
    suggested: None
    SARS-CoV-2 pseudotyped lentiviruses were prepared by co-transfecting the HEK 293T cell line with the SARS-CoV-2 614G spike (D614G) or SARS-CoV-2 Beta spike (L18F, D80A, D215G, K417N, E484K, N501Y, A701V, 242-244 del
    HEK 293T
    suggested: None
    Software and Algorithms
    SentencesResources
    SARS-CoV-2 spike WGS and phylogenetic analysis: Whole genome sequencing (WGS) of SARS-CoV-2 was performed from nasopharyngeal swabs.
    WGS
    suggested: None
    Raw reads from the Illumina COVIDSeq protocol were assembled using the Exatype NGS SARS-CoV-2 pipeline v1.6.1, (https://sars-cov-2.exatype.com/).
    SARS-CoV-2
    suggested: (BioLegend Cat# 946101, RRID:AB_2892515)
    Samples were acquired on a BD Fortessa flow cytometer and analyzed using FlowJo (v10.8
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis: Statistical analyses were performed in Prism (v9; GraphPad Software Inc, San Diego, CA, USA).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.12.26.21268380 on medRxiv