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Favorable vaccine-induced SARS-CoV-2–specific T cell response profile in patients undergoing immune-modifying therapies
Martin Qui, … , Antonio Bertoletti, Ennaliza Salazar
Martin Qui, … , Antonio Bertoletti, Ennaliza Salazar
Published May 10, 2022
Citation Information: J Clin Invest. 2022;132(12):e159500. https://doi.org/10.1172/JCI159500.
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Clinical Research and Public Health Immunology Article has an altmetric score of 14

Favorable vaccine-induced SARS-CoV-2–specific T cell response profile in patients undergoing immune-modifying therapies

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Abstract

BACKGROUND Patients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the effect of such therapies on vaccine-induced T cell responses.METHODS We longitudinally characterized humoral and spike-specific T cell responses in patients with inflammatory bowel disease (IBD), who were on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors, and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing 2-dose COVID-19 mRNA vaccination.RESULTS We demonstrate that a spike-specific T cell response was not only induced in treated patients with IBD at levels similar to those of healthy individuals, but also sustained at higher magnitude for up to 6 months after vaccination, particularly in those treated with TNF inhibitor therapy. Furthermore, the spike-specific T cell response in these patients was mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile.CONCLUSION Despite the humoral response defects, patients under immune-modifying therapies demonstrated a favorable profile of vaccine-induced T cell responses that might still provide a layer of COVID-19 protection.FUNDING This study was funded by the National Centre for Infectious Diseases (NCID) Catalyst Grant (FY2021ES) and the National Research Fund Competitive Research Programme (NRF-CRP25-2020-0003).

Authors

Martin Qui, Nina Le Bert, Webber Pak Wo Chan, Malcolm Tan, Shou Kit Hang, Smrithi Hariharaputran, Jean Xiang Ying Sim, Jenny Guek Hong Low, Weiling Ng, Wei Yee Wan, Tiing Leong Ang, Antonio Bertoletti, Ennaliza Salazar

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Figure 7

IL-10 delineates T cell cytokine response profile of individuals undergoing immune-modifying therapies.

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IL-10 delineates T cell cytokine response profile of individuals undergo...
(A and B) Dot plots with median (middle bar) and interquartile range (whiskers) (A) of IL-10 concentrations (pg/mL) from S pool–stimulated whole-blood supernatants of the 2 study cohorts collected at different time points and (B) of HCs and patients with IBD grouped by treatment 3 and 6 months after completing their 2-dose vaccination. Shaded red regions denote the area under the threshold for a positive test. Statistical analyses were performed by (A) Wilcoxon’s signed-rank test or (B) Kruskal-Wallis and Dunn’s test, with P values indicated above the comparison line when significant (P ≤ 0.05). Geometric means (GMean; AU/mL) and number of data points (n) are indicated below each group. (C) UMAP projections based on IL-10, IFN-γ, and IL-2 quantities measured from each donor time point. Images on the top row display each point filled according to log10-transformed cytokine quantities (pg/mL). Images on the bottom row display points filled according to study cohort at the respective time point. A shape is drawn enclosing a region mostly containing points with IL-10 values of greater than 10 pg/mL. (D) Dot plots with median (middle bar) and interquartile range (whiskers) of IL-10+CD4+ cell frequencies of CD4+ from HCs (n = 12) or donors with IBD on TNFi (with or without AM, n = 21) or nTNFi therapy (n = 12). Statistical analysis was performed by Wilcoxon’s signed-rank test, with P values indicated above the comparison line when significant (P ≤ 0.05). For all graphs, the shaded red region denotes responses below background levels (denoted with 0).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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