Rapid induction of antigen-specific CD4 + T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination

  1. Mark M. Painter
  2. Divij Mathew
  3. Rishi R. Goel
  4. Sokratis A. Apostolidis
  5. Ajinkya Pattekar
  6. Oliva Kuthuru
  7. Amy E. Baxter
  8. Ramin S. Herati
  9. Derek A. Oldridge
  10. Sigrid Gouma
  11. Philip Hicks
  12. Sarah Dysinger
  13. Kendall A. Lundgreen
  14. Leticia Kuri-Cervantes
  15. Sharon Adamski
  16. Amanda Hicks
  17. Scott Korte
  18. Josephine R. Giles
  19. Madison E. Weirick
  20. Christopher M. McAllister
  21. Jeanette Dougherty
  22. Sherea Long
  23. Kurt D’Andrea
  24. Jacob T. Hamilton
  25. Michael R. Betts
  26. Paul Bates
  27. Scott E. Hensley
  28. Alba Grifoni
  29. Daniela Weiskopf
  30. Alessandro Sette
  31. Allison R. Greenplate
  32. E. John Wherry

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Abstract

The SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses in healthy individuals following mRNA vaccination. Vaccination induced rapid near-maximal antigen-specific CD4 + T cell responses in all subjects after the first vaccine dose. CD8 + T cell responses developed gradually after the first and second dose and were variable. Vaccine-induced T cells had central memory characteristics and included both Tfh and Th1 subsets, similar to natural infection. Th1 and Tfh responses following the first dose predicted post-boost CD8 + T cell and neutralizing antibody levels, respectively. Integrated analysis of 26 antigen-specific T cell and humoral responses revealed coordinated features of the immune response to vaccination. Lastly, whereas booster vaccination improved CD4 + and CD8 + T cell responses in SARS-CoV-2 naïve subjects, the second vaccine dose had little effect on T cell responses in SARS-CoV-2 recovered individuals. Thus, longitudinal analysis revealed robust T cell responses to mRNA vaccination and highlighted early induction of antigen-specific CD4 + T cells.

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    SciScore for 10.1101/2021.04.21.440862: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    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: 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.

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  2. Version published to 10.1101/2021.04.21.440862v1 on bioRxiv