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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

Jason Neidleman, Xiaoyu Luo, Matthew McGregor, Guorui Xie, Victoria Murray, Warner C. Greene, Sulggi A. Lee, Nadia R. Roan
doi: https://doi.org/10.1101/2021.05.12.443888
Jason Neidleman
1Gladstone Institute of Virology, San Francisco, CA, USA
2Department of Urology, University of California, San Francisco, CA, USA
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Xiaoyu Luo
1Gladstone Institute of Virology, San Francisco, CA, USA
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Matthew McGregor
1Gladstone Institute of Virology, San Francisco, CA, USA
2Department of Urology, University of California, San Francisco, CA, USA
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Guorui Xie
1Gladstone Institute of Virology, San Francisco, CA, USA
2Department of Urology, University of California, San Francisco, CA, USA
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Victoria Murray
3Zuckerberg San Francisco General Hospital and the University of California, San Francisco, CA, USA
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Warner C. Greene
1Gladstone Institute of Virology, San Francisco, CA, USA
4Departments of Medicine, and Microbiology and Immunology, University of California, San Francisco, CA, USA
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Sulggi A. Lee
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  • For correspondence: nadia.roan@gladstone.ucsf.edu sulggi.lee@ucsf.edu
Nadia R. Roan
1Gladstone Institute of Virology, San Francisco, CA, USA
2Department of Urology, University of California, San Francisco, CA, USA
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  • For correspondence: nadia.roan@gladstone.ucsf.edu sulggi.lee@ucsf.edu
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵# Lead contact

  • The inclusion of 3 additional participants each analyzed at 3 timepoints each, for a total of 45 additional specimens.

  • https://doi.org/10.7272/Q60R9MMK

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 29, 2021.
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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
Jason Neidleman, Xiaoyu Luo, Matthew McGregor, Guorui Xie, Victoria Murray, Warner C. Greene, Sulggi A. Lee, Nadia R. Roan
bioRxiv 2021.05.12.443888; doi: https://doi.org/10.1101/2021.05.12.443888
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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
Jason Neidleman, Xiaoyu Luo, Matthew McGregor, Guorui Xie, Victoria Murray, Warner C. Greene, Sulggi A. Lee, Nadia R. Roan
bioRxiv 2021.05.12.443888; doi: https://doi.org/10.1101/2021.05.12.443888

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