mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status

  1. Jason Neidleman
  2. Xiaoyu Luo
  3. Matthew McGregor
  4. Guorui Xie
  5. Victoria Murray
  6. Warner C Greene
  7. Sulggi A Lee  Is a corresponding author
  8. Nadia R Roan  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Gladstone Institute of Virology, United States

Abstract

While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naïve and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naïve individuals, the second dose boosted the quantity and altered the phenotypic properties of SARS-CoV-2-specific T cells, while in convalescents the second dose changed neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naïve vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx. These results provide reassurance that vaccine-elicited T cells respond robustly to emerging viral variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2-specific T cells compared to their infection-naïve counterparts.

Data availability

The original datasets are available through Dryad: https://doi.org/10.7272/Q60R9MMK

The following data sets were generated

Article and author information

Author details

  1. Jason Neidleman

    Department or Urology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaoyu Luo

    Gladstone Institute of Virology, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthew McGregor

    Gladstone Institute of Virology, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Guorui Xie

    Department or Urology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Victoria Murray

    Department or Urology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Warner C Greene

    Gladstone Institute of Virology, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9896-8615
  7. Sulggi A Lee

    Medicine, University of California, San Francisco, San Francisco, United States
    For correspondence
    Sulggi.lee@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1560-2250
  8. Nadia R Roan

    Gladstone Institute of Virology, San Francisco, United States
    For correspondence
    nadia.roan@gladstone.ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5464-1976

Funding

Sandler Foundation (Program for Breakthrough Biomedical Research)

  • Nadia R Roan

Fast Grants (2164,2208,2160)

  • Sulggi A Lee
  • Nadia R Roan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study was approved by the University of California, San Francisco (IRB # 20-30588). All participants provided informed consent, and consent to publish, before participation.

Copyright

© 2021, Neidleman et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jason Neidleman
  2. Xiaoyu Luo
  3. Matthew McGregor
  4. Guorui Xie
  5. Victoria Murray
  6. Warner C Greene
  7. Sulggi A Lee
  8. Nadia R Roan
(2021)
mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status
eLife 10:e72619.
https://doi.org/10.7554/eLife.72619

Share this article

https://doi.org/10.7554/eLife.72619

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