Robust T Cell Responses to the Pfizer/Biontech Vaccine Compared to Infection and Evidence of Attenuated Cd8+ T Cell Responses Due to Covid-19

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-CoV2 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 SARSCoV-2 infection decreased 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.Funding Information: This work was supported by grants from the Howard Hughes Medical Institute and NIAID grant AI057229 to MMD. Additional support was provided by the Bill and Melinda Gates Foundation to MMD (OPP1113682, Center for Human Systems Immunology) and ITI-YIA to VM. Further funds were provided by the Sean N Parker Center, the Sunshine Foundation, and U01 AI140498 to MM and KCN.Declaration of Interests: The other authors declare that they have no competing interests.Ethics Approval Statements: The BNT162b2 vaccine donors were recruited for the study with informed consent. The study was approved by the Stanford University Institutional Review Board (IRB 8629) and was conducted with full compliance of Good Clinical Practice as per the Code of Federal Regulations.The COVID-19 patient sample collection for this study was done at the Stanford Occupational Health under an IRB approved protocol (Protocol Director, Nadeau). All participants consented prior to enrolling in the study.Peripheral blood mononuclear cells (PBMCs) from healthy donors were obtained from the Stanford Blood Center according to our IRB approved protocol.