Immunity
Volume 56, Issue 4, 11 April 2023, Pages 864-878.e4
Journal home page for Immunity

Article
Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection

https://doi.org/10.1016/j.immuni.2023.03.005Get rights and content
Under a Creative Commons license
open access

Highlights

  • CD8+ and CD4+ T cell responses characterized using SARS-CoV-2 pMHC spheromers

  • CD8+ and CD4+ T cell response kinetics are decoupled after mRNA vaccination

  • Reduced peripheral CD8+ T cell responses after infection compared with mRNA vaccination

  • Previous exposure limits peripheral CD8+ T cell responses after mRNA vaccination

Summary

T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using “spheromer” peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4+ (HLA-DRB115:01/S191) and CD8+ (HLA-A02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring 1 week post the second vaccination (boost), whereas CD8+ T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that previous infection can influence the T cell response to vaccination.

Keywords

SARS-CoV-2
COVID-19
spheromer
peptide-MHC multimer
Pfizer/BioNTech mRNA vaccine
antigen-specific T cell responses
peripheral CD8+ T cell responses
peripheral CD4+ T cell responses
SARS-CoV-2 variants of concern

Data and code availability

The data supporting the findings of this study are available within the published article and summarized in the corresponding tables, figures, and supplemental materials. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

10

These authors contributed equally

11

Lead contact