TY - JOUR
T1 - In-depth analysis of SARS-CoV-2–specific T cells reveals diverse differentiation hierarchies in vaccinated individuals
AU - Li, Li
AU - Muftuoglu, Muharrem
AU - Liang, Shaoheng
AU - Basyal, Mahesh
AU - Jiangxing, L. V.
AU - Akdogan, Mehmet Emin
AU - Chen, Ken
AU - Andreeff, Michael
AU - Flowers, Christopher R.
AU - Parmar, Simrit
N1 - Funding Information:
We thank MD Anderson North Campus Flow Cytometry and Cellular Imaging Core Facility for support with flow cytometry (NIH National Cancer Institute CA16672). This study was supported by the sponsored research funding grant support from Cellenkos Inc (award 54964).
Publisher Copyright:
© 2022, Li Li et al.
PY - 2022/4/8
Y1 - 2022/4/8
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.156559
DO - 10.1172/jci.insight.156559
M3 - Article
C2 - 35230977
AN - SCOPUS:85128249119
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 7
M1 - e156559
ER -