Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection
Fei Gao, Vamsee Mallajosyula, Prabhu S. Arunachalam, Kattria van der Ploeg, Monali Manohar, Katharina Röltgen, Fan Yang, Oliver F. Wirz, Ramona A. Hoh, Emily Haraguchi, Ji-Yeun Lee, Richard A. Willis, Vasanthi Ramachandiran, Jun Li, Karan R. Kathuria, Chunfeng Li, Alexandra S. Lee, Mihir Shah, Sayantani Sindher, Joseph C. González, John D. Altman, Taia T. Wang, Scott D. Boyd, Bali Pulendran, Prasanna Jagannathan, Kari C. Nadeau, Mark M. Davis
Abstract
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 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.