Robust T cell responses to Pfizer vaccine compared to infection and evidence of attenuated peripheral CD8+ T cell responses due to COVID-19, 2023

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 to mRNA vaccination.
• Prior 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-DRB1∗15:01/S191) and CD8+ (HLA-A∗02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring one week post the second vaccination (boost), whereas CD8+ T cells peaked two weeks later. These peripheral T cell responses were elevated compared to COVID-19 patients. We also found that prior SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that prior infection can influence the T cell response to vaccination.

https://www.cell.com/immunity/fulltext/S1074-7613(23)00125-5

 

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