Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals

  1. Andrew D Redd
  2. Alessandra Nardin
  3. Hassen Kared
  4. Evan M Bloch
  5. Brian Abel
  6. Andrew Pekosz
  7. Oliver Laeyendecker
  8. Michael Fehlings
  9. Thomas C Quinn
  10. Aaron AR Tobian

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Abstract

There is a growing concern that ongoing evolution of SARS-CoV-2 could lead to variants of concern (VOC) that are capable of avoiding some or all of the multi-faceted immune response generated by both prior infection or vaccination, with the recently described B.1.1.529 (Omicron) VOC being of particular interest. Peripheral blood mononuclear cell samples from PCR-confirmed, recovered COVID-19 convalescent patients (n=30) infected with SARS-CoV-2 in the United States collected in April and May 2020 who possessed at least one or more of six different HLA haplotypes were selected for examination of their anti-SARS-CoV-2 CD8+ T-cell responses using a multiplexed peptide-MHC tetramer staining approach. This analysis examined if the previously identified viral epitopes targeted by CD8+ T-cells in these individuals (n=52 distinct epitopes) are mutated in the newly described Omicron VOC (n=50 mutations). Within this population, only one low-prevalence epitope from the Spike protein restricted to two HLA alleles and found in 2/30 (7%) individuals contained a single amino acid change associated with the Omicron VOC. These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC, and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time.

Importance

The newly identified Omicron variant of concern contains more mutations than any of the previous variants described to date. In addition, many of the mutations associated with the Omicron variant are found in areas that are likely bound by neutralizing antibodies, suggesting that the first line of immunological defense against COVID-19 may be compromised. However, both natural infection and vaccination develop T-cell based responses, in addition to antibodies. This study examined if the parts of the virus, or epitopes, targeted by the CD8+ T-cell response in thirty individuals who recovered from COVID-19 in 2020 were mutated in the Omicron variant. Only one of 52 epitopes identified in this population contained an amino acid that was mutated in Omicron. These data suggest that the T-cell immune response in previously infected, and most likely vaccinated individuals, should still be effective against Omicron.

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    SciScore for 10.1101/2021.12.06.471446: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Ethics: All study participants provided written informed consent, and this study was approved by the Johns Hopkins Institutional Review Board.
    IRB: Ethics: All study participants provided written informed consent, and this study was approved by the Johns Hopkins Institutional Review Board.
    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 several limitations for this analysis. The results are based on a relatively small samples size of individuals who were all from the United States. Additionally, we examined the CD8+ T-cell responses in previously infected but not vaccinated individuals, and it is possible that the T-cell responses in this later group are more limited and therefore more susceptible to escape. However, work examining T-cell responses from vaccinees has demonstrated a strong CD4+ and CD8+ T-cell responses in these individuals, suggesting that similar trends should be seen in this population as well[2,10]. While it is unknown what specific immune response, or more likely combination of responses, provides optimum protection against SARS-CoV-2 infection and COVID-19, it almost certainly includes a broad and robust CD8+ T-cell response. These data build on the previous analysis of the initial VOC, and confirm that while SARS-CoV-2 has demonstrated a continued pattern of ongoing evolution this has not resulted in any meaningful accumulation of CD8+ T-cell escape mutations[7]. These data also suggest that existing CD8+ T-cell responses from a previous SARS-CoV-2 infection, and most likely from vaccination as well, will still recognize the Omicron VOC and should provide a significant level of protection against COVID-19.

    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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  2. Version published to 10.1101/2021.12.06.471446 on bioRxiv