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

• Published in: Immunity (Cambridge, Mass.) Vol. 56; no. 4; pp. 864 - 878.e4
• Main Authors: Gao, Fei, Mallajosyula, Vamsee, Arunachalam, Prabhu S., van der Ploeg, Kattria, Manohar, Monali, Röltgen, Katharina, Yang, Fan, Wirz, Oliver, Hoh, Ramona, Haraguchi, Emily, Lee, Ji-Yeun, Willis, Richard, Ramachandiran, Vasanthi, Li, Jiefu, Kathuria, Karan Raj, Li, Chunfeng, Lee, Alexandra S., Shah, Mihir M., Sindher, Sayantani B., Gonzalez, Joseph, Altman, John D., Wang, Taia T., Boyd, Scott D., Pulendran, Bali, Jagannathan, Prasanna, Nadeau, Kari C., Davis, Mark.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.04.2023
• Subjects: Antibodies, Viral; antigen-specific T cell responses; BNT162 Vaccine; CD8-Positive T-Lymphocytes; COVID-19; Humans; peptide-MHC multimer; peripheral CD4+ T cell responses; peripheral CD8+ T cell responses; Pfizer/BioNTech mRNA vaccine; SARS-CoV-2; SARS-CoV-2 variants of concern; spheromer; Vaccination; Vaccines; COVID-19; peripheral CD8+ T cell responses; peptide-MHC multimer; SARS-CoV-2; antigen-specific T cell responses; SARS-CoV-2 variants of concern; peripheral CD4+ T cell responses; Pfizer/BioNTech mRNA vaccine; spheromer; peripheral CD4(+) T cell responses; peripheral CD8(+) T cell responses
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2023.03.005

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. [Display omitted] •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 Our understanding of T cell responses in COVID-19 and vaccination is incomplete. Gao et al. examine SARS-CoV-2-specific T cell responses to infection and vaccination, revealing disparate kinetics between CD4+ and CD8+ T cells. Furthermore, compared with vaccination alone, circulating CD8+ T cells are attenuated during infection and in subsequent vaccination.