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T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis
Asia-Sophia Wolf, … , Gro Owren Nygaard, Siri Mjaaland
Asia-Sophia Wolf, … , Gro Owren Nygaard, Siri Mjaaland
Published May 9, 2023
Citation Information: JCI Insight. 2023;8(12):e165111. https://doi.org/10.1172/jci.insight.165111.
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Research Article COVID-19 Immunology

T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis

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Abstract

Immune responses in people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies, including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators, attenuate Ab responses after vaccination. Evaluation of cellular responses after vaccination, therefore, is of particular importance in these populations. In this study, we used flow cytometry to analyze CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy control study participants and pwMS receiving 5 different DMTs. Although pwMS receiving rituximab and fingolimod therapies had low Ab responses after both 2 and 3 vaccine doses, T cell responses in pwMS taking rituximab were preserved after a third vaccination, even when an additional dose of rituximab was administered between vaccine doses 2 and 3. PwMS taking fingolimod had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that, even in the absence of robust Ab responses, vaccination can generate immune responses in pwMS.

Authors

Asia-Sophia Wolf, Anthony Ravussin, Marton König, Mathias H. Øverås, Guri Solum, Ingrid Fadum Kjønstad, Adity Chopra, Trygve Holmøy, Hanne F. Harbo, Silje Watterdal Syversen, Kristin Kaasen Jørgensen, Einar August Høgestøl, Jon Torgils Vaage, Elisabeth G. Celius, Fridtjof Lund-Johansen, Ludvig A. Munthe, Gro Owren Nygaard, Siri Mjaaland

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Figure 1

Responses after 2 vaccine doses in pwMS on DMTs.

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Responses after 2 vaccine doses in pwMS on DMTs.
Individuals are grouped...
Individuals are grouped by DMT (healthy control participants [HC], and patients with MS who were treated with alemtuzumab [ALEM], cladribine [CLAD], natalizumab [NTZ], fingolimod [FIN], and rituximab [RTX]). (A) BAU values after 2 doses of vaccine. Responses below the lower limit of detection are shown as 0.5 BAU/mL; titers <5 BAU/mL are considered negative, 5–20 BAU/mL as very (V.) weak positives, 20–200 BAU/mL as weak positives, and >200 BAU/mL as positives. Individuals are shown as separate points; the box indicates median and IQR, whiskers indicate minimum and maximum values. Statistical analyses by Kruskal-Wallis test comparing DMT groups with HC with the Benjamini-Hochberg correction for multiple comparisons. (B) CD4 T cell (CD40L+ TNF-α+) and (C) CD8 T cell responses (IFN-γ+ and/or TNF-α+) to spike peptides before (V0) and after (V2) 2 doses of vaccine. Responses with zero events are plotted at 0.001% to indicate nonresponses. Samples from the same individual before and after vaccination are paired with a line. Statistical comparisons by Wilcoxon 2-tailed paired t tests. *P < 0.05, **P < 0.01, with the Holm-Šídák method for multiple comparisons. Patient numbers for each group are indicated along the x axis.

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