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In-depth analysis of SARS-CoV-2–specific T cells reveals diverse differentiation hierarchies in vaccinated individuals
Li Li, Muharrem Muftuoglu, Shaoheng Liang, Mahesh Basyal, Jiangxing LV, Mehmet Emin Akdogan, Ken Chen, Michael Andreeff, Christopher R. Flowers, Simrit Parmar
Li Li, Muharrem Muftuoglu, Shaoheng Liang, Mahesh Basyal, Jiangxing LV, Mehmet Emin Akdogan, Ken Chen, Michael Andreeff, Christopher R. Flowers, Simrit Parmar
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Research Article COVID-19 Immunology

In-depth analysis of SARS-CoV-2–specific T cells reveals diverse differentiation hierarchies in vaccinated individuals

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Abstract

SARS-CoV-2 vaccines pose as the most effective approach for mitigating the COVID-19 pandemic. High-degree efficacy of SARS-CoV-2 vaccines in clinical trials indicates that vaccination invariably induces an adaptive immune response. However, the emergence of breakthrough infections in vaccinated individuals suggests that the breadth and magnitude of vaccine-induced adaptive immune response may vary. We assessed vaccine-induced SARS-CoV-2 T cell response in 21 vaccinated individuals and found that SARS-CoV-2–specific T cells, which were mainly CD4+ T cells, were invariably detected in all individuals but the response was varied. We then investigated differentiation states and cytokine profiles to identify immune features associated with superior recall function and longevity. We identified SARS-CoV-2–specific CD4+ T cells were polyfunctional and produced high levels of IL-2, which could be associated with superior longevity. Based on the breadth and magnitude of vaccine-induced SARS-CoV-2 response, we identified 2 distinct response groups: individuals with high abundance versus low abundance of SARS-CoV-2–specific T cells. The fractions of TNF-α– and IL-2–producing SARS-CoV-2 T cells were the main determinants distinguishing high versus low responders. Last, we identified that the majority of vaccine-induced SARS-CoV-2 T cells were reactive against non-mutated regions of mutant S-protein, suggesting that vaccine-induced SARS-CoV-2 T cells could provide continued protection against emerging variants of concern.

Authors

Li Li, Muharrem Muftuoglu, Shaoheng Liang, Mahesh Basyal, Jiangxing LV, Mehmet Emin Akdogan, Ken Chen, Michael Andreeff, Christopher R. Flowers, Simrit Parmar

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Figure 4

Phenotypic and evolutionary traits of vaccine-induced SARS-CoV-2–specific T cells.

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Phenotypic and evolutionary traits of vaccine-induced SARS-CoV-2–specifi...
(A) Heatmap shows the expression of cytokines and differentiation markers of SARS-CoV-2–specific CD4+ and CD8+ T cells. The color bar indicates subsets producing different combinations of cytokines, and the scale bar shows the scaled expression level. (B) Dot plot shows the expression of CCR7, CD62L, and CD45RA in concatenated SARS-CoV-2–specific CD4+ (left) and CD8+ (right) T cells from 21 vaccinated individuals. (C) SARS-CoV-2–specific CD4+ (middle) and CD8+ (right) T cells and equal number of SARS-CoV-2– T cells (left) were pooled and subjected to UMAP dimension reduction, and differentiation state of each single cell was inferred through pseudotime analysis. Pseudotime values are shown for each single cell. (D) Trend plots (left) and lines (right) show the expression levels of differentiation markers and cytokines along the pseudotime. Color scale indicates the scaled expression levels.

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