mRNA vaccination boosts S-specific T cell memory and promotes expansion of CD45RAint TEMRA-like CD8+ T cells in COVID-19 recovered individuals

• Type of Material: Article
• Authors: Koshlan Mayer-Blackwell, Fred Hutchinson Cancer Research Center; Heeju Ryu, Fred Hutchinson Cancer Research Center; Amy S. Codd, Fred Hutchinson Cancer Research Center; K. Rachael Parks, Fred Hutchinson Cancer Research Center; Hugh R. MacMillan, Fred Hutchinson Cancer Research Center; Kristen W. Cohen, Fred Hutchinson Cancer Research Center; Terri L. Stewart, Fred Hutchinson Cancer Research Center; Aaron Seese, Fred Hutchinson Cancer Research Center; Maria P. Lemos, Fred Hutchinson Cancer Research Center; Stephen C. De Rosa, Fred Hutchinson Cancer Research Center; Julie L. Czartoski, Fred Hutchinson Cancer Research Center; Zoe Moodie, Fred Hutchinson Cancer Research Center; Long T. Nguyen, Fred Hutchinson Cancer Research Center; Donald J. McGuire, Emory University; Rafi Ahmed, Emory University; Andrew Fiore-Gartland, Fred Hutchinson Cancer Research Center; M. Juliana McElrath, Fred Hutchinson Cancer Research Center; Evan W. Newell, Fred Hutchinson Cancer Research Center
• Language: English
• Date: 2023-08-15
• Publisher: CellPress
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.xcrm.2023.101149
• Title of Journal or Parent Work: Cell Reports Medicine
• Volume: 4
• Issue: 8
• Start Page: 101149
• End Page: 101149
• Grant/Funding Information: The research reported in this publication was supported in part by COVID supplements from the National Institute of Allergy and Infectious Diseases and the Office of the Director of the National Institutes of Health under award numbers UM1AI068618 and UM1AI069481 (M.J.M.), the NIH Human Immunology Project Consortium (U19AI128914) (M.J.M.), Immunological Memory to COVID-19 Supplement (R.A.), Paul G. Allen Family Foundation Award #12931 (M.J.M.), Basic Science Research Program through the National Research Foundation of Korea (NRF-2020R1A6A3A03037852, to H.R.), IIRC post-doctoral fellowship (224990-99, to H.R.), the Seattle COVID-19 Cohort Study (Fred Hutchinson Cancer Center) (M.J.M.), Fred Hutchinson Cancer Center New Development funds (to E.W.N.), and The Andy Hill Endowment Distinguished Researcher CARE fund (E.W.N.).
• Keywords: CyTOF; CD8-Positive T-Lymphocytes; Humans; Epitopes; Memory T Cells; Vaccination; CD8 T cells; CD4 T cells; vaccination; COVID-19; SARS-CoV-2; Leukocyte Common Antigens
• Research Categories: Biology, Virology; Biology, Cell

Abstract

SARS-CoV-2 infection and mRNA vaccination both elicit spike (S)-specific T cell responses. To analyze how T cell memory from prior infection influences T cell responses to vaccination, we evaluated functional T cell responses in naive and previously infected vaccine recipients. Pre-vaccine S-specific responses are predictive of subsequent CD8+ T cell vaccine-response magnitudes. Comparing baseline with post-vaccination TCRβ repertoires, we observed large clonotypic expansions correlated with the frequency of spike-specific T cells. Epitope mapping the largest CD8+ T cell responses confirms that an HLA-A∗03:01 epitope was highly immunodominant. Peptide-MHC tetramer staining together with mass cytometry and single-cell sequencing permit detailed phenotyping and clonotypic tracking of these S-specific CD8+ T cells. Our results demonstrate that infection-induced S-specific CD8+ T cell memory plays a significant role in shaping the magnitude and clonal composition of the circulating T cell repertoire after vaccination, with mRNA vaccination promoting CD8+ memory T cells to a TEMRA-like phenotype.