tetano
Editor, Senior Moderator
JCI Insight
. 2022 Mar 1;e156559.
doi: 10.1172/jci.insight.156559. Online ahead of print.
In-depth analysis of SARS-CoV-2-specific T cells reveals diverse differentiation hierarchies in vaccinated individuals
Li Li[SUP] 1 [/SUP], Muharrem Muftuoglu[SUP] 2 [/SUP], Shaoheng Liang[SUP] 3 [/SUP], Mahesh Basyal[SUP] 2 [/SUP], Jiangxing Lv[SUP] 1 [/SUP], Mehmet E Akdogan[SUP] 4 [/SUP], Ken Chen[SUP] 3 [/SUP], Michael Andreeff[SUP] 2 [/SUP], Simrit Parmar[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines pose as the most effective approach for mitigating COVID-19 pandemic. High-degree efficacy of SARS-CoV-2 vaccines in clinical trials indicates that vaccination invariably induces an adaptive immune response in vaccine recipients. However, the emergence of breakthrough infections in vaccinated individuals suggest that the breadth and magnitude vaccine-induced adaptive immune response may varies. We assessed vaccine-induced SARS-CoV-2 T-cell response in twenty-one vaccinated individuals and found that SARS-CoV-2 specific T-cells were invariably detected in all individuals. However, the magnitude and breadth of SARS-CoV-2 specific T-cell response varied. Vaccination induced mainly a CD4+ T-cell dominant SARS-CoV-2 specific immune response and the frequencies of SARS-CoV-2 specific T-cell varied across vaccinated individuals. To gain insights into whether SARS-CoV-2 vaccines can induce a long-lived T-cell immune response we investigated differentiation states and cytokine profiles to identify immune features associated with superior recall function and longevity. We identified distinct hierarchically organized differentiation states and cytokine expression patterns. SARS-CoV-2 specific CD4+ T-cells were polyfunctional and produced high levels of IL-2, which could be associated with superior longevity. Stratifying the vaccinated individuals based on the breadth and magnitude of vaccine-induced SARS-CoV-2 response identified two distinct response groups: individuals with high abundance vs low abundance of SARS-CoV-2 T-cells. The fractions of TNF-a and IL-2 producing SARS-CoV-2 T-cells were the main determinants distinguishing high vs low responders. Lastly, we identified the majority of vaccine-induced SARS-CoV-2 T-cells were reactive against conserved regions of mutant S-protein, suggesting that vaccine-induced SARS-CoV-2 T-cells could provide continued protection against emerging variants-of-concern.
Keywords: Adaptive immunity; COVID-19; Immunology.
. 2022 Mar 1;e156559.
doi: 10.1172/jci.insight.156559. Online ahead of print.
In-depth analysis of SARS-CoV-2-specific T cells reveals diverse differentiation hierarchies in vaccinated individuals
Li Li[SUP] 1 [/SUP], Muharrem Muftuoglu[SUP] 2 [/SUP], Shaoheng Liang[SUP] 3 [/SUP], Mahesh Basyal[SUP] 2 [/SUP], Jiangxing Lv[SUP] 1 [/SUP], Mehmet E Akdogan[SUP] 4 [/SUP], Ken Chen[SUP] 3 [/SUP], Michael Andreeff[SUP] 2 [/SUP], Simrit Parmar[SUP] 1 [/SUP]
Affiliations
- PMID: 35230977
- DOI: 10.1172/jci.insight.156559
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines pose as the most effective approach for mitigating COVID-19 pandemic. High-degree efficacy of SARS-CoV-2 vaccines in clinical trials indicates that vaccination invariably induces an adaptive immune response in vaccine recipients. However, the emergence of breakthrough infections in vaccinated individuals suggest that the breadth and magnitude vaccine-induced adaptive immune response may varies. We assessed vaccine-induced SARS-CoV-2 T-cell response in twenty-one vaccinated individuals and found that SARS-CoV-2 specific T-cells were invariably detected in all individuals. However, the magnitude and breadth of SARS-CoV-2 specific T-cell response varied. Vaccination induced mainly a CD4+ T-cell dominant SARS-CoV-2 specific immune response and the frequencies of SARS-CoV-2 specific T-cell varied across vaccinated individuals. To gain insights into whether SARS-CoV-2 vaccines can induce a long-lived T-cell immune response we investigated differentiation states and cytokine profiles to identify immune features associated with superior recall function and longevity. We identified distinct hierarchically organized differentiation states and cytokine expression patterns. SARS-CoV-2 specific CD4+ T-cells were polyfunctional and produced high levels of IL-2, which could be associated with superior longevity. Stratifying the vaccinated individuals based on the breadth and magnitude of vaccine-induced SARS-CoV-2 response identified two distinct response groups: individuals with high abundance vs low abundance of SARS-CoV-2 T-cells. The fractions of TNF-a and IL-2 producing SARS-CoV-2 T-cells were the main determinants distinguishing high vs low responders. Lastly, we identified the majority of vaccine-induced SARS-CoV-2 T-cells were reactive against conserved regions of mutant S-protein, suggesting that vaccine-induced SARS-CoV-2 T-cells could provide continued protection against emerging variants-of-concern.
Keywords: Adaptive immunity; COVID-19; Immunology.