mRNA vaccination boosts S-specific T cell memory and promotes expansion of CD45RAint TEMRA-like CD8+ T cells in COVID-19 recovered individuals
Koshlan Mayer-Blackwell, Heeju Ryu, Amy Codd, K. Rachael Parks, Hugh R. MacMillan, Kristen W. Cohen, Terri L. Stewart, Aaron Seese, Maria P. Lemos, Stephen C. De Rosa, Julie Czartoski, Zoe Moodie, Long Thành Nguyễn, Donald J. McGuire, Rafi Ahmed, Andrew Fioré-Gartland, M. Juliana McElrath, Evan W. Newell
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 T EMRA -like phenotype.