Booster mRNA vaccination post-SARS-CoV-2 infection enhances functional qualities of T cell immunity

Abstract

T cells are critical to providing protection from severe COVID-19. However, whether repeated SARS-CoV-2 vaccination post-infection fuels T cell exhaustion or reshapes functionality remains debated. Here, we sampled SARS-CoV-2 convalescent donors of different COVID-19 disease severity before and after subsequent mRNA vaccination to determine the functional consequences of hybrid immunity. Using combined single-cell protein and transcriptional analysis of T cells targeting different regions of the SARS-CoV-2 genome, we identified that spike-specific T cells increased in magnitude but, notably, also gained improved polyfunctional characteristics. In contrast, T cell responses targeting non-spike proteins diminished with time and functionally remained unchanged. Elevated IFN-γ expression was a common hallmark of CD4+ and CD8+ T cell responses in mRNA-vaccinated individuals after SARS-CoV-2 infection. These responses were founded on both pre-expanded and newly detected CD8+ T cell clones after vaccination. Elevated IFN-γ production and magnitude of SARS-CoV-2-specific CD4+ and CD8+ T cells were also found in patients with B cell abnormalities (chronic lymphocytic leukemia; CLL) after booster mRNA vaccination (four doses). Collectively, these data demonstrate limited signs of functional exhaustion and instead cumulative benefits of booster vaccination post-infection, increasing the quantity and quality of cell-mediated immunity.

High-resolution kinetics and cellular determinants of antibody response to SARS-CoV-2 over two years after COVID-19 vaccination

“…All participants had detectable T cell responses for up to 6 months after the booster dose, consistent with previous research 15 . In parallel with other studies, T cell responses after COVID-19 vaccination were mainly directed to the S antigen 49 , with the secretion of IFN-γ, followed by IL-2 50,51 . SARS-CoV-2-specific CD4 + T cells had a central and effector memory phenotype [52][53][54] , while CD8 + T cells were predominantly naïve-like and terminal effector memory [54][55][56] .…”

pan-MHC and cross-Species Prediction of T Cell Receptor-Antigen Binding

“…To further validate the potential use of pMTnet-omni to monitor the functional relevance of the evolving TCR repertoire in various contexts, we analyzed patients after COVID-19 vaccination. Specifically, we studied a set of 7 patients who recovered from prior SARS-CoV-2 infections and later received mRNA-based COVID-19 vaccines 46 ( Fig. 4a ).…”

“…Table 6 , TCR-sequencing data can be accessed in the receptor data table of DBAI with accession numbers from Receptor_00000000000001 to Receptor_00000000000113, and the cytokine profiling data can be found in FigShare under the DOI: https://doi.org/10.6084/m9.figshare.24570136.v2. The COVID-19 vaccination data (processed scRNA-seq, TCR-seq, and metadata) were obtained from the original publication 46 . The Visium-TCR-seq data were obtained from www.ncbi.nlm.nih.gov/sra/?term=PRJNA742564 and www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE179572.…”

“…The scRNA-seq/TCR-seq and the patients’ metadata were obtained from Curtis et al 45 . scRNA-seq analyses followed our general procedure described in the “ 10X scRNA-seq/scTCR-seq data analyses ” section below.…”