Robust T cell responses to the Pfizer/BioNTech vaccine compared to infection and evidence of attenuated CD8+ T cell responses due to COVID-19

Abstract

Abstract The COVID-19 pandemic has resulted in rapid development of several novel vaccine platforms, including the mRNA-based Pfizer/BioNTech vaccine. As of October 2022, more than 3.8 billion Pfizer/BioNTech vaccines were administrated to people in 180 countries. Meanwhile, the total number of COVID-19 cases has reached 627 million globally. We recently developed a new antigen-specific T cell staining tool— ”spheromer”that is able to label T cells more efficiently and capture a broader swath of the repertoire than any other available platform. Using spheromers loaded with SARS-CoV-2 peptides, we applied a panel covers 49 epitopesspanning the entire genome to characterize the magnitude and durability of antigen-specific T cell responses at single-epitope resolution. Using very sensitive “spheromer” peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in very robust peripheral blood responses to predicted SARS-CoV-2 spike peptides bound to either class-I or class-II MHC alleles. These peaked at 9.8% and 7.5% for the dominant CD4+ (HLA-DRB1*15:01/S191) and CD8+ (HLA-A*02/S691) T cell epitopes. Interestingly, the 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 didn’t peak until two weeks later. These responses were much higher than in COVID-19 patients. We also found that prior SARS-CoV-2 infectiondecreased the CD8+ T cell response post vaccination by 2.4 to 41.4-fold at peak, and that the remaining cells were less responsive, suggesting that the virus can profoundly damage an individuals’ CD8+ T cell response. 1. Howard Hughes Medical Institute and NIAID grant AI057229 to Mark.M.Davis; 2. Bill and Melinda Gates Foundation grant OPP1113682, Center for Human Systems Immunology, to Mark.M.Davis; 3. U01 AI140498 to to Mark.M.Davis.